Pharmacology RSS : Gourt

Finalists Nominated For The 2008 European Biotechnica Award

The three finalists of the 2008 EUROPEAN BIOTECHNICA AWARD have been determined. The biotechnology companies nominated are Cambridge-based Astex Therapeutics Limited (UK), GENEART AG from Regensburg (Germany) and immatics biotechnologies GmbH based in Tübingen (Germany). The prize, worth EUR 100,000, is awarded to innovative European biotechnology and life sciences companies.

Manhattan Research Announces Top 10 Product Sites Visited By Physicians

Diabetes treatment brand sites from Januvia, Actos, Byetta, and Avandia are among the top pharmaceutical product websites in terms of primary care physician visitation, according to a new from pharmaceutical and healthcare market research company Manhattan Research (www.manhattanresearch.com). Breaking into this year's top product site list are Actos, Actonel, Amitiza, and Aciphex, proving to be successful in increasing physician awareness online.

Anthera Pharmaceuticals Advances Global Development Strategy For Varespladib In Patients With Acute Coronary Syndrome

Anthera Pharmaceuticals Inc., a privately held biopharmaceutical company developing anti-inflammatory drugs, announced the initiation of the FRANCIS (Fewer Recurrent Acute coronary events with Near-term Cardiovascular Inflammation Suppression) clinical trial designed to examine the impact of varespladib when administered to patients within 96 hours of an Acute Coronary Syndrome (ACS) event.

New Trial To Evaluate Nexavar® As Adjuvant Therapy In Liver Cancer

Bayer HealthCare Pharmaceuticals, Inc. and Onyx Pharmaceuticals, Inc. announced the start of a Phase III study with Nexavar� (sorafenib) tablets in liver cancer. The randomized, double-blind, placebo-controlled study is evaluating Nexavar as an adjuvant therapy for patients with hepatocellular carcinoma (HCC), or primary liver cancer. An adjuvant treatment is given as an additional systemic therapy after the initial tumor treatment, e.g.

Bayer HealthCare And Regeneron Announce VEGF Trap-Eye Achieved Durable Improvement In Vision Over 52 Weeks In A Phase 2

Bayer HealthCare AG and Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) announced that patients with wet age-related macular degeneration (AMD) receiving VEGF Trap-Eye in a Phase 2 extension study on a PRN (as needed) dosing schedule continued to show highly significant improvements at 52 weeks in the primary and key secondary endpoints of retinal thickness (an anatomic measure of treatment effect) and vision gain.

Patients Taking Cymbalta® Experienced Reduced Chronic Low Back Pain In New Study

Data from a new study suggest that Cymbalta (duloxetine HCl) 60-120 mg once daily significantly reduced chronic low back pain, as measured by the Brief Pain Inventory (BPI) 24-hour average pain score, compared with placebo.(1) Results from the double-blind, 13-week, placebo-controlled study of 236 patients were presented today at the annual congress of the European Federation of Neurological Societies (EFNS) in Madrid, Spain.

Society Of Plastics Engineers' 2008 Research Award

Dr. Dilhan M. Kalyon, Professor of Chemical Engineering and Director of the Highly Filled Materials Institute at Stevens Institute of Technology, has won the Society of Plastics Engineers' 2008 Research Award (in Memory of John C. Moricoli). Kalyon received his B.Eng. in Chemical Engineering in Ankara, Turkey, and his M. Eng. and Ph.D. in Chemical Engineering/Polymers at McGill University in Montreal, Canada.

Research And Markets: The Top 10 World's Leading Pharmaceutical Companies: Pfizer

Research and Markets has announced the addition of the "The Top 10 World's Leading Pharmaceutical Companies: Pfizer" report to their offering. In a highly dynamic and fragmented pharmaceutical market, besieged by intense competition, rapid pace of technological innovations and the uncertainty regarding future government regulations, the ability to anticipate new competitive product introductions and marketing strategies is particularly important...

Chairman Announced For Eyeforpharma's Patient Adherence And Persistence USA Summit 2008

Tickets are now on sale for eyeforpharma's Patient Adherence, Persistence and Compliance USA Summit, October 23-24, Boston and are selling out fast. Last year the event sold out with over 200 delegates, a ratio of 80% pharma and over 90% positive feedback. The chairman has been announced recently as Daryl J.

Helping The Medicine Go Down

Getting little Doug and Debbie to take a spoonful of medicine is more than just a rite of passage for frustrated parents. Children's refusal to swallow liquid medication - and their tendency to vomit it back up - is an important public health problem that means longer or more serious illness for thousands of kids each year. In the case of HIV and AIDS pediatrics, missing a dose can be a life or death scenario.

FDA Approves ALOXI(R) (Palonosetron HCl) Capsules For Prevention Of Acute Chemotherapy Induced Nausea And Vomiting

Eisai Corporation of North America and its partner Helsinn Healthcare SA announced that the U.S. Food and Drug Administration (FDA) has approved a new oral formulation of ALOXI(R) (palonosetron hydrochloride) for the prevention of chemotherapy-induced nausea and vomiting (CINV). ALOXI Capsules 0.

Cymbalta Receives European Approval For The Treatment Of Generalised Anxiety Disorder

Eli Lilly and Co (NYSE: LLY) and Boehringer Ingelheim have announced that the European Commission has approved the use of Cymbalta(R) (duloxetine) for the treatment of Generalised Anxiety Disorder (GAD). This approval -- the fourth for duloxetine in Europe -- was issued on 28 July following an initial positive opinion issued by the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) on 26 June 2008.

Indevus Pharmaceuticals Announces Completion Of Enrollment In Phase III Trial Of PRO 2000

Indevus Pharmaceuticals, Inc. (Nasdaq: IDEV) announced the completion of enrollment in Protocol MDP 301, a Phase III clinical trial of PRO 2000, the Company's candidate vaginal microbicide for the prevention of HIV and other sexually transmitted infections.

Human Genome Sciences Completes Enrollment In Randomized Phase 2 Trial Of HGS-ETR1 In Non-Small Cell Lung Cancer

Human Genome Sciences, Inc. (Nasdaq: HGSI) announced that it has completed the enrollment and initial dosing of patients in a randomized Phase 2 trial of HGS-ETR1 (mapatumumab) in combination with the chemotherapy agents paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC).

Head-to-Head Study Showed Prasugrel Statistically Superior To Clopidogrel In Reducing Recurrent Cardiovascular Events

A new, pre-specified analysis of the landmark Phase III head-to-head TRITON-TIMI 38 study showed patients who took prasugrel for acute coronary syndromes (ACS) managed with an artery-opening procedure known as percutaneous coronary intervention (PCI) and had survived their first cardiov

FDA Requires Additional Information On DORIBAX For Treatment Of Hospital-Acquired Pneumonia

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) announced that the U.S. Food and Drug Administration (FDA) requires additional information before it will approve the company's New Drug Application (NDA) for DORIBAX(TM) (doripenem for injection) for the treatment of hospital-acquired pneumonia, also known as nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP).

Bayer And Onyx Begin Enrollment In STORM Trial Studying Nexavar As Adjuvant Therapy For Patients With Liver Cancer

Bayer HealthCare Pharmaceuticals, Inc. and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) announced the companies have begun enrolling patients in the STORM Sorafenib as Adjuvant Treatment in the Prevention of Recurrence of Hepatocellular Carcinoma trial.

Ardea Biosciences Advances Lead Product Candidate For The Treatment Of Gout, RDEA594, Into Phase 1 Clinical Trial

Ardea Biosciences, Inc. (Nasdaq: RDEA) announced that the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom has authorized a Phase 1 study evaluating RDEA594 in normal healthy volunteers. RDEA594 is the Company's lead product candidate for the treatment of gout.

Telik's Proteasome Inhibitor Program Meets A Preclinical Development Milestone

Telik, Inc. (Nasdaq: TELK) announced that its novel small molecule proteasome inhibitor program met a preclinical development milestone by demonstrating anticancer activity in preclinical models of human leukemia. The proteasome is an important cellular structure necessary for the growth and function of cancer cells and inhibition of the proteasome has been shown to promote cell cycle arrest and cancer cell death or apoptosis.

The New MagNA Pure LC 2.0 System: New Design And Improved Performance Meet A Proven Nucleic Acid Isolation Technology

A fast, flexible, and reliable isolation of pure nucleic acids from various sample materials is crucial for sensitive molecular analysis by PCR, RT-PCR, sequencing, arrays etc. In addition, automation of nucleic acid isolation is becoming increasingly important for reproducibility and to reduce experimental error. During the last years, demands regarding hardware design, software, and operating system have been increasing. The new MagNA Pure LC 2.

States Consider Legislation To Restrict Access To Physician Prescribing Information For Data Mining Companies

A number of states have begun to consider legislation that would restrict access to physician prescribing information for data mining companies as part of a "backlash against pharmaceutical marketing efforts," the AP/Arizona Republic reports. Data mining companies, such as

Bristol-Myers Squibb And PDL BioPharma Enter Global Alliance To Develop Novel Treatment For Multiple Myeloma

Bristol-Myers Squibb Company (NYSE: BMY) and PDL BioPharma, Inc. (NASDAQ: PDLI) today announced an agreement for the global development and commercialization of PDL BioPharma's anti-CS1 antibody, elotuzumab, previously known as HuLuc63, currently in Phase I development for multiple myeloma.

Enobia Pharma Initiates Clinical Testing Of Enzyme Replacement Therapy To Treat Hypophosphatasia

Enobia Pharma, an emerging biotech company focused on developing novel therapeutics for serious bone disorders, announced that the first patient in its clinical program for hypophosphatasia has been dosed. Enobia is investigating Enzyme Replacement Therapy (ERT) with ENB-0040 for the treatment of this rare and often crippling genetic bone disorder for which there is no approved treatment.

BioVex Announces Regulatory Clearance To Commence A Clinical Study With ImmunoVEX HSV2; A Vaccine Candidate For Genital Herpes

BioVex Inc, a biotechnology company developing clinical stage treatments for cancer and the prevention of infectious disease, announced the UK Medicines and Healthcare products Regulatory Agency (MHRA) has accepted BioVex's Clinical Trial Application to conduct a Phase I clinical study testing the safety and immunogenicity of its lead infectious disease candidate for genital herpes, ImmunoVEX HSV2.

PTC124 Shows Promising Activity In Cystic Fibrosis; Phase 2 Proof-of-Concept Data Published In The Lancet

New phase 2 data published today in The Lancet show that the investigational oral drug PTC124 demonstrates activity in nonsense-mutation cystic fibrosis (CF). The data show that treatment with PTC124 results in statistically significant improvements in the chloride channel function of patients with nonsense-mutation CF.

Mood Disorders: A Practical Guide, 2nd Edition (November)

Dependence of Time to Reach Steady-State on the Length of Dosage Interval (October)

Our Daily Meds (October)

Assessing the Reporting and Scientific Quality of Meta-Analyses of Randomized Controlled Trials of Treatments for Anxiety Disorders(October)

BACKGROUND: Meta-analyses of randomized controlled trials (RCTs) constitute the highest level of evidence, but their usefulness depends on their quality. OBJECTIVE: To assess the reporting and scientific quality of meta-analyses of RCTs on treatments for anxiety disorders. METHODS: Criteria for peer-reviewed, full-text retrieval included meta-analyses of RCTs of drugs versus active ingredient placebo, standard care, or psychotherapy. Sample populations were required to meet Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases and Related Health Problems diagnostic criteria for anxiety disorders. Two reviewers independently searched EMBASE, EBM Reviews, Ovid MEDLINE, Ovid HealthSTAR, and International Pharmaceutical Abstracts from inception to August 2007. Search terms included meta-analysis, randomized controlled trials, anxiety, anxiolytic, anti-depressant/antidepressant, and pharmacotherapy, without language restrictions. References and reviews were searched manually. Quality was assessed independently by 2 raters, using the Quality of Reporting of Meta-analyses (QUOROM) and the Overview Quality Assessment Questionnaire (OQAQ). The QUOROM was used to assess the reporting quality of the study, using an 18-item checklist, and the scientific quality was assessed with the OQAQ's 10-item checklist. Kendall's measured interrater reliability with statistical significance at p less than or equal to 0.01. Means and standard deviations described the overall quality. A time series analysis was performed. RESULTS: A total of 136 titles and abstracts were reviewed; 48 were retrieved, including 6 from the manual search. Thirty-two were excluded (not pooled analyses, inappropriate condition/treatment, duplications), leaving 16 studies published between 1995 and 2007. Agreement was high: = 0.801 (p < 0.01) for QUOROM and 0.834 (p < 0.01) for OQAQ. QUOROM quality scored 61% ± 19%. Overall, the results sections of the studies scored lowest, while the introduction and discussion sections scored highest. The overall scientific quality was 58% ± 28%. Most studies appropriately linked results to primary objectives but did not report how bias was avoided or how study validity was assessed. Quality increased nonsignificantly over time. CONCLUSIONS: Reporting/scientific quality was considered less than fair-to-good. Stakeholders should strive for higher scientific quality of meta-analyses.

Pharmacokinetics and Pharmacodynamics of Intranasal Versus Intravenous Fentanyl in Patients with Pain after Oral Surgery(October)

BACKGROUND: Fentanyl, a short-acting synthetic opioid, has a pharmacokinetic profile suited to fast relief of brief episodic pain. OBJECTIVE: To characterize the pharmacokinetic-pharmacodynamic correlation of intranasal and intravenous fentanyl in opioid-naïve patients undergoing third molar extraction. METHODS: A double-blind, double-dummy, crossover design study was conducted, with patients randomized to receive 1 of 4 fentanyl doses (75, 100, 150, or 200 µg) by both the intravenous and intranasal routes. Venous fentanyl concentrations were determined for up to 180 minutes and pain scores were recorded up to 240 minutes postdose. Duration of effect and time to rescue medication were also recorded. RESULTS: The pharmacokinetics of intravenous fentanyl reflected a 2-compartment model with a clearance of approximately 1.5 L/min. There was moderate (<50%) between-subject variability (BSV; %CV [coefficient of variation]) in the systemic kinetics of fentanyl. Bioavailability of intranasal fentanyl was 89%, following first-order absorption, with a lag of approximately 5 minutes and a half-life of approximately 6.5 minutes. Interpatient absorption variability was approximately 30% BSV for all absorption parameters. Intranasal versus intravenous administration led to a delayed mean fentanyl time to maximum concentration (13 vs 6 min) and lower maximum concentration (1.2 vs 2.0 ng/mL). Analgesic effect lagged behind the venous fentanyl concentration, with a half-life of approximately 2.5 minutes as described by a fractional sigmoid maximum drug effect dynamic model. The concentration-analgesia relationship was steep, with a 50% effective concentration of 0.46 ng/mL (Hill coefficient 3.5). Intranasal onset and offset of analgesia were slightly delayed, principally due to the delay and lag in systemic absorption, with slightly lower peak analgesic effect, compared with intravenous fentanyl. Duration of effect was directly related to intranasal fentanyl dose, with pain scores returning to predose values at approximately 120 minutes (75 µg) to approximately 240 minutes (200 µg) after a single dose. CONCLUSIONS: Intranasal fentanyl showed kinetic and dynamic properties that are desirable for the management of acute, episodic (breakthrough) pain.

Sibutramine-Associated QT Interval Prolongation and Cardiac Arrest (October)

OBJECTIVE: To report on a probable association between sibutramine and QT interval prolongation leading to ventricular fibrillation and cardiac arrest. CASE SUMMARY: A previously well 51-year-old woman with obesity but no other relevant past medical history or cardiac risk factors was prescribed sibutramine (initial dose 10 mg daily, increased to 15 mg daily after 10 wk). Four months after initiation of therapy, the woman developed ventricular fibrillation and was successfully resuscitated. On admission, an electrocardiogram (ECG) demonstrated sinus tachycardia without any ischemic changes and a prolonged QTc interval (545 msec). A subsequent coronary angiogram revealed normal coronary arteries and no other abnormalities. Her QTc interval returned to normal (432 msec) by day 2 and remained within normal limits (<440 msec) thereafter. Due to a favorable neurologic recovery and the absence of any cardiac structural abnormality, the patient was readmitted for implantation of an automatic implantable cardioverter-defibrillator on day 35 and remained well from a cardiac and neurologic standpoint at a 2-year follow-up examination. DISCUSSION: Sibutramine acts centrally to inhibit noradrenaline, dopamine, and serotonin reuptake, thereby sharing similar actions of other QT interval-prolonging drugs. Therefore, sibutramine might be anticipated to also share a tendency to QT interval prolongation. The current prescribing information for sibutramine does not specifically list any precautions or adverse reactions related to QT interval prolongation. QT interval prolongation associated with sibutramine in this case is considered probable based on the Naranjo probability scale. CONCLUSIONS: Clinicians prescribing sibutramine should monitor their patients for ECG abnormalities and be cautious in coprescribing drugs known to prolong the QT interval.

Duloxetine-Associated Tachycardia (October)

OBJECTIVE: To report a case of symptomatic tachycardia that was successfully treated with propranolol in a patient receiving duloxetine. CASE SUMMARY: A 26-year-old man presented with episodes of fatigue, tachycardia, diaphoresis, and chest pain approximately 2 months after the initiation of duloxetine 20 mg/day for dysthymic disorder. Cardiac workup including echocardiogram, exercise treadmill testing, and Holter monitoring was negative, except for tachycardia (heart rate 110-120 beats/min). Duloxetine was withheld, and the patient's heart rate returned to normal in less than a week. Duloxetine was restarted at the same dosage, and tachycardia returned within 2 days. Propranolol was added to the treatment regimen to lower the heart rate. Because of therapeutic failure of other antidepressants, duloxetine was continued because of its beneficial effects on mood. DISCUSSION: One published case report describing tachycardia in association with duloxetine in 2 heart failure patients was found in a MEDLINE search (1966-July 2008). Increased blood pressure and heart rate have been reported in duloxetine trials. The proposed mechanism for duloxetine-induced tachycardia is its effects on norepinephrine, which impact the cardiovascular system. Use of the Naranjo probability scale indicated duloxetine as a probable cause of this patient's tachycardia. CONCLUSIONS: Clinicians should be aware of the possibility of clinically significant tachycardia in patients receiving duloxetine, even in low doses.

Potential Aluminum Exposure from Parenteral Nutrition in Patients with Acute Kidney Injury(October)

BACKGROUND: Patients' exposure to and potential toxicity from aluminum in parenteral nutrition (PN) formulations is an important concern of healthcare providers. OBJECTIVE: To determine the potential for aluminum toxicity caused by PN in hospitalized adults who have risk factors of both acute kidney injury and PN. METHODS: Adults who required PN and had a serum creatinine (SCr) level at least 1.5 times greater than the admission SCr on the first day of PN were studied in a retrospective fashion. Protein was administered based on whether hemodialysis was being used (0.6-1 g/kg/day without hemodialysis; 1.2-1.5 g/kg/day with hemodialysis). Aluminum exposure was determined for each patient by multiplying the volume of each PN component by its concentration of aluminum. Unpaired t-tests, Fisher's exact test, and analysis of variance were used for statistical analysis. Data are presented as mean ± SD. RESULTS: Thirty-six patients (aged 50.4 ± 20.4 y; weight 90.2 ± 32.8 kg) were studied. Initial serum urea nitrogen and SCr were 47 ± 23 and 3.3 ± 1.4 mg/dL, respectively. Twelve patients received hemodialysis. The mean aluminum exposure was 3.8 ± 2 µg/kg/day in the 36 patients. Of these, 29 had safe calculated aluminum exposure (<5 µg/kg/day) and 7 had high calculated aluminum exposure (>5 µg/kg/day). Patients with safe aluminum exposure had significantly higher SCr levels than did those with high aluminum exposure (3.5 ± 1.5 vs 2.2 ± 0.7 mg/dL; p < 0.04). Patients with high aluminum exposure received significantly more aluminum from calcium gluconate compared with those who had safe aluminum exposure (357 ± 182 vs 250 ± 56 µg/day; p > 0.02). Limitations of the study include its retrospective design, which resulted in calculated versus direct measurement of aluminum. CONCLUSIONS: Using our calculations, we believe that most patients with acute kidney injury who require PN do not receive excessive exposure to aluminum from the PN formulation, despite having 2 risk factors (acute kidney injury, PN) for aluminum toxicity.

Posaconazole: An Oral Triazole with an Extended Spectrum of Activity (October) (CE)

OBJECTIVE: To summarize the published clinical data on posaconazole, critically review the New Drug Application data submitted to the Food and Drug Administration, and provide information critical for evaluation and formulary positioning. DATA SOURCES: Reported investigations were identified from MEDLINE (1966-June 30, 2008), bibliographies of manuscripts, www.clinicaltrials.gov, and www.fda.gov. STUDY SELECTION AND DATA EXTRACTION: English-language articles were selected. All available in vitro, animal, clinical, and human studies describing the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, safety, and adverse events of posaconazole were reviewed. DATA SYNTHESIS: Posaconazole is an oral broad-spectrum triazole with activity against many yeasts and molds. Resistance to posaconazole has been reported, but has been rare to date. Posaconazole, in doses of 200 mg 3 times daily, reduced breakthrough invasive fungal infections (OR 0.30; 95% CI 0.12 to 0.71) and aspergillosis incidence (OR 0.31; 95% CI 0.13 to 0.75) in patients receiving hematopoietic stem-cell transplants compared with those receiving fluconazole. Similarly, the same regimen of posaconazole reduced invasive fungal infections (95% CI -9.7 to -2.5) and aspergillosis (CI not reported, p < 0.001) when compared with fluconazole and itraconazole in neutropenic patients. Posaconazole is noninferior to fluconazole for treatment of oropharyngeal candidiasis (95% CI -6.6 to 5.0), but necessity for this indication remains unclear, as many other treatment options exist. Smaller investigations have analyzed use of posaconazole for patients requiring salvage or alternative treatment for zygomycosis, fusariosis, cryptococcal meningitis, coccidioidomycosis, and histoplasmosis. Studies are needed to clarify efficacy for such expanded use, and therapeutic drug monitoring may improve outcomes. The most common adverse effects associated with the use of posaconazole include headache, fever, nausea, vomiting, and diarrhea. CONCLUSIONS: Posaconazole appears to be a valuable and promising addition to the antifungal armamentarium for prophylaxis and treatment of various fungal processes. At this time, posaconazole should probably be reserved for prophylaxis in patients at high risk for invasive fungal infection, as salvage therapy in refractory or resistant infections, or for patients with intolerance to other therapies.

Topiramate for Alcohol Dependence (October)

OBJECTIVE: To evaluate the evidence for the use of topiramate for alcohol dependence. DATA SOURCES: MEDLINE (1966-June 2008) and Cochrane Database (2008, Issue 1) searches were conducted using the search terms alcohol dependence and topiramate. Bibliographies of selected articles were examined for additional data sources. STUDY SELECTION AND DATA EXTRACTION: English-language, randomized, controlled trials evaluating topiramate for treatment of alcohol dependence in humans were selected for review. Three randomized controlled trials and 2 reanalyses were identified. Findings pertaining to efficacy and safety were extracted. DATA SYNTHESIS: Evidence suggests that topiramate antagonizes excitatory glutamate receptors, inhibits dopamine release, and enhances inhibitory -aminobutyric acid function. These mechanisms may be significant in the treatment of alcohol dependence. Controlled trials have described the use of topiramate, titrated up to 300 mg daily, for alcohol dependence, and have reported decreases in drinking behavior and improvements in quality of life. Adverse effects associated with topiramate included abnormal skin sensation, dizziness, taste perversion, anorexia, pruritus, and difficulty with memory and concentration. In one of the reviewed trials, adverse effects did not account for an increased withdrawal rate. However, in another, when topiramate was titrated over a shortened time period, an increased withdrawal rate was seen. Recently, topiramate has been reported to increase suicide risk, primarily in patients with epilepsy. No cases of suicide were recorded in the alcohol dependence trials. CONCLUSIONS: Results of published trials are promising, showing efficacy for drinking outcomes and quality of life as well as general safety. However, additional larger, longer-term trials are needed to establish the optimal patient type that would benefit most from topiramate treatment in addition to dosing, duration of treatment, and tolerability of topiramate for alcohol dependence. At this time, data are insufficient to support using topiramate in conjunction with brief weekly compliance counseling as a first-line agent for alcohol dependence.

Delayed-Onset Neutropenia with Divalproex Sodium (October)

OBJECTIVE: To report the development of neutropenia in a patient after almost 8 years of being stabilized on delayed-release divalproex sodium (DVPX). CASE SUMMARY: A 45-year-old man had been maintained on DVPX for nearly 8 years, with serum valproic acid concentrations of 85-128 mg/L and normal white blood cell (WBC) counts and absolute neutrophil counts (ANCs). Five months prior to the development of neutropenia (defined as ANC <1800 cells/µL), the patient's DVPX dosage was decreased by 250 mg to 1250 mg every morning and 1500 mg every evening. After 2 months of that regimen, the DVPX dosage was increased back to 1500 mg twice daily. Three months after that increase, the patient's WBC count dropped to 3.7 x 103/µL and ANC was 1199 cells/µL. Although the ANC was below 1800 cells/µL, he showed no physical manifestations consistent with neutropenia. DVPX was discontinued, and 2 weeks later the patient's WBC count was 7.2 x 103/µL and ANC was 2290 cells/µL. DISCUSSION: Although a complete blood cell count with differential is a commonly accepted form of therapeutic drug monitoring with DVPX, the monitoring is considered most necessary to identify dose-related thrombocytopenia. However, neutropenia has been rarely associated with the use of DVPX and could contribute to the development of different types of infection, including those of a bacterial, viral, or fungal origin. Although neutropenia is generally mild in severity, potentially severe DVPX-associated neutropenia can occur any time during the course of therapy, although it is most common within the first few months of treatment. In this case, DVPX was the probable cause of the neutropenia, according to the Naranjo probability scale. However, this case of neutropenia is atypical with respect to the timeframe in which it developed and was identified. Although the documented laboratory findings suggest neutropenia, the patient did not experience any clinical complications as a result. The late onset of the patient's neutropenia is unlike other cases that have been documented in the literature. CONCLUSIONS: Hematologic therapeutic drug monitoring continues to be clinically important regardless of whether the patient is early in therapy or even years later in the course. In this patient, continued regular therapeutic drug monitoring identified a suspected drug-related complication and the medication was able to be discontinued without the development of clinical complications.

Propylene Glycol-Induced Lactic Acidosis in a Patient Receiving Continuous Infusion Pentobarbital (October)

OBJECTIVE: To report a case of probable propylene glycol (PG) toxicity in a patient receiving continuous infusion of pentobarbital for refractory status epilepticus. CASE SUMMARY: A 59-year-old woman with a declining mental status was admitted to the intensive care unit for management of status epilepticus. After failing to achieve the therapeutic endpoint of electroencephalogram burst suppression with a continuous infusion of propofol, the sedative regimen was changed to continuous infusion of pentobarbital. The patient received a loading dose of 450 mg (5 mg/kg), and the maintenance infusion was titrated to a dose of 10 mg/kg/h to achieve burst suppression. Twelve hours after the pentobarbital infusion was started, the patient developed an anion gap metabolic acidosis, elevated serum lactate level, hyperosmolality, and increased osmolal gap. The pentobarbital infusion was discontinued, and the patient's acidosis and hyperosmolality resolved. DISCUSSION: Pentobarbital contains 40% v/v of PG, which was thought to be a potential source of the patient's metabolic derangements. Reports of toxicity with drugs containing PG, particularly intravenous lorazepam, have been well described in the literature. What we describe, however, is one of few reports involving intravenous pentobarbital. The Naranjo probability scale supports a probable drug-related adverse event in our patient. CONCLUSIONS: PG toxicity is a potential complication associated with intravenous pentobarbital. Practitioners should be aware of the PG content of pentobarbital and should be familiar with the signs and symptoms associated with PG toxicity.

Drug Information Handbook for Oncology: A Complete Guide to Combination Chemotherapy Regimens, 7th Edition (October)

Oral Glutamine for the Prevention of Chemotherapy-Induced Peripheral Neuropathy (October)

OBJECTIVE: To evaluate the role of glutamine in the reduction of peripheral neuropathy associated with neurotoxic chemotherapy. DATA SOURCES: Relevant literature was accessed through PubMed (1990-May 2008), using the search terms glutamine, chemotherapy, peripheral neuropathy, neurotoxicity, safety, paclitaxel, platinum compounds, and vinca alkaloids. References in the identified articles were also reviewed for pertinent information. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the role of oral glutamine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN) were included. Studies regarding the role of glutamine in the reduction of other radiation- and chemotherapy-related toxicities, such as mucositis, cardiotoxicity, diarrhea, and cachexia, were excluded. DATA SYNTHESIS: CIPN is a significant adverse effect associated with neurotoxic chemotherapy, particularly with taxanes, platinum compounds, and vinca alkaloids. There is no standard therapy for the treatment of this dose-limiting reaction. Glutamine is a nonessential amino acid that is thought to have a neuroprotective role, possibly due to the upregulation of nerve growth factor. Two studies revealed that oral glutamine was effective in reducing peripheral neuropathy associated with high-dose paclitaxel, as evidenced by a reduction in numbness, dysesthesias, and motor weakness, as well as a smaller loss of vibratory sensation. Another study found that glutamine effectively reduced peripheral neuropathy in patients with colorectal cancer being treated with oxaliplatin, thereby decreasing the need for an oxaliplatin dose reduction. However, data are limited by small sample sizes in these studies and the lack of placebo-controlled, randomized clinical trials. CONCLUSIONS: Larger, well-designed, placebo-controlled trials assessing both safety and efficacy of oral glutamine are warranted before this agent can be definitively recommended for the prevention of CIPN in patients treated with high-dose paclitaxel or oxaliplatin.

Comparison of Oral Aspirin Versus Topical Applied Methyl Salicylate for Platelet Inhibition (October)

BACKGROUND: Oral acetylsalicylic acid (aspirin) is the primary antiplatelet therapy in the treatment of acute myocardial infarction and acute coronary syndrome. Methyl salicylate (MS; oil of wintergreen) is compounded into many over-the-counter antiinflammatory muscle preparations and has been shown to inhibit platelet aggregation locally and to be absorbed systemically. OBJECTIVE: To assess the ability of topically applied MS to inhibit systemic platelet aggregation for patients who are unable to tolerate oral drug therapy. METHODS: A randomized, prospective, blinded, crossover study was conducted in 9 healthy men, aged 30-46 years. All subjects ingested 162 mg of aspirin or applied 5 g of 30% MS preparation to their anterior thighs. There was a minimum 2-week washout period between study arms. Blood and urine were collected at baseline and at 6 hours. An aggregometer measured platelet aggregation over time against 5 standard concentrations of epinephrine, and a mean area under the curve (AUC) was calculated. Urinary metabolites of thromboxane B2 were measured by a standard enzyme immunoassay. Differences in and between groups at baseline and 6 hours were tested by the Wilcoxon signed-rank test. RESULTS: Baseline platelet aggregation did not differ significantly between the 2 arms of the study (median AUC [% aggregation*min]; binominal confidence intervals): aspirin 183; 139 to 292 versus MS 197; 118 to 445 (p = 0.51). Both aspirin and MS produced statistically significant platelet inhibition; aspirin decreased the AUC from 183; 139 to 292 to 85; 48 to 128 (p = 0.008) and MS decreased the AUC from 197; 118 to 445 to 112; 88 to 306 (p = 0.011). No significant difference was detected between baseline and 6-hour thromboxane levels for either aspirin (p = 0.779) or MS (p = 0.327). CONCLUSIONS: Topical MS and oral aspirin both significantly decrease platelet aggregation in healthy human volunteers.

Maribavir: A Novel Antiviral Agent with Activity Against Cytomegalovirus (October)

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of maribavir, a novel antiviral agent in the benzimidazole drug class. DATA SOURCES: Articles were identified through searches of MEDLINE (January 1998-July 2008). Abstracts from recent scientific meetings and the manufacturer were also included. STUDY SELECTION AND DATA EXTRACTION: All English-language in vitro and in vivo studies and abstracts evaluating maribavir were reviewed and considered for inclusion. All human studies were included. DATA SYNTHESIS: Maribavir has significant activity against both human cytomegalovirus (CMV) and Epstein-Barr virus, but not other herpesviruses. Unlike ganciclovir, which needs to be phosphorylated by UL 97 kinase to become an active inhibitor of DNA polymerase, maribavir directly inhibits UL 97 kinase. UL 97 kinase is an early viral gene product involved in viral DNA elongation, DNA packaging, and egress or shedding of capsids from viral nuclei. Maribavir has also been found to be effective against ganciclovir-resistant CMV strains. Maribavir differs from current CMV antiviral agents in its adverse event profile. Maribavir is not associated with nephrotoxicity or hematologic toxicities, but has been associated with taste disturbances. In February 2007, maribavir was granted Food and Drug Administration orphan drug status for prevention of CMV viremia and diseases in at-risk populations. Maribavir Phase 2 trials in stem-cell transplant recipients have been completed, and there are ongoing Phase 3 trials in stem-cell and organ transplant recipients CONCLUSIONS: Maribavir may be an option for treatment of ganciclovir-resistant CMV infections. Its bioavailability is greater than that of oral ganciclovir, but less than that of valganciclovir. No differences in pharmacokinetics were seen in renally impaired patients, although dialysis-dependent patients were not evaluated. Maribavir is not associated with hematologic toxicities; however, the high prevalence of taste disturbances may limit its tolerability.

Thiazolidinediones in Type 2 Diabetes: A Cardiology Perspective (October)

OBJECTIVE: To examine the cardiovascular effects of thiazolidinediones (TZDs), discuss concerns regarding this drug class and its relation to heart failure (HF) and myocardial infarction (MI), and address the clinical implications of HF and MI. DATA SOURCES: Literature was accessed through MEDLINE (1979-April 2008) using the search terms type 2 diabetes mellitus, thiazolidinediones, cardiovascular events, heart failure, myocardial infarction, and edema. Reviews, meta-analyses, clinical trials, observational studies (case-control, cohort), and descriptive studies (case reports, case series) were included. STUDY SELECTION AND DATA EXTRACTION: All articles that were written in English and identified from the data sources were reviewed. DATA SYNTHESIS: The American Diabetes Association recommends metformin as first-line therapy for type 2 diabetes, with the subsequent addition of a TZD, sulfonylurea, or insulin if the target is not met. Beyond glucose lowering, TZDs improve various factors associated with cardiovascular risk. Whether the effects translate into beneficial cardiovascular outcomes is controversial. In PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events), pioglitazone did not produce a significant reduction in the primary endpoint that included a composite of coronary and vascular deaths, but the secondary composite endpoint of all-cause mortality, MI, or stroke was significantly reduced. Concerns related to HF have led to warnings in the labeling of TZDs. The drugs are contraindicated in patients with New York Heart Association Class III or IV HF. Rosiglitazone, but not pioglitazone, is associated with an increased risk of myocardial ischemic events, although the absolute magnitude is extremely small. CONCLUSIONS: Although the glycemic efficacy of TZDs is comparable to that of metformin, adverse effects and higher costs make TZDs less appealing for initial therapy. Among the TZDs, pioglitazone should be considered based on cardiovascular safety data. In combination with metformin, pioglitazone may be particularly beneficial for patients with diabetes and metabolic syndrome. For patients on rosiglitazone who are achieving glycemic goals and tolerating the therapy without apparent complications, rosiglitazone may be continued.

Desvenlafaxine: Another "Me Too" Drug? (October) (CE)

OBJECTIVE: To compare desvenlafaxine with its parent drug, venlafaxine, to determine the usefulness of this new medication. DATA SOURCES: Information was obtained through a MEDLINE search (1966-June 2008) and from published abstracts. Search terms included desvenlafaxine, O-desmethylvenlafaxine, Pristiq, major depressive disorder, and venlafaxine. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts pertaining to desvenlafaxine and venlafaxine were considered for inclusion. Preference was given to human data. DATA SYNTHESIS: Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor and is the active metabolite of the antidepressant venlafaxine. The recommended dose is 50 mg daily, based on the efficacy and safety data of 50, 100, 150, 200, and 400 mg of desvenlafaxine. The response and remission rates of depression at 8 weeks for the 50-mg dose are 51-63% and 31-45%, respectively. These rates are comparable with those seen with venlafaxine (58% and 45%, respectively). Adverse effects are also similar to those of venlafaxine, with the most common being insomnia, somnolence, dizziness, and nausea. The decreased potential of CYP2D6 activity with desvenlafaxine compared with the parent drug may be a potential advantage in patients on other medications metabolized via this enzymatic pathway. Also, desvenlafaxine tablets are less expensive than extended-release (XR) venlafaxine, which may decrease healthcare costs in the short term. However, venlafaxine XR is expected to go off patent in 2010. CONCLUSIONS: With the overall similarity between these 2 drugs and the potential lack of cost savings, the need for desvenlafaxine and its ultimate utility in treating major depressive disorder appears to be insignificant.

Candesartan Cilexetil Effectively Reduces Blood Pressure in Hypertensive Children (October)

BACKGROUND: The angiotensin-receptor blocker candesartan cilexetil is a well-tolerated antihypertensive agent with demonstrated benefits in adults with hypertension. However, there are few data supporting its use in children with hypertension. OBJECTIVE: To determine the efficacy and tolerability of candesartan cilexetil in the treatment of pediatric hypertension. METHODS: In an open-label, uncontrolled pilot study, hypertensive pediatric patients were eligible for participation if untreated systolic and/or diastolic blood pressure (BP) exceeded the 95th percentile for sex, age, and height. Patients underwent a 7-day washout period prior to initiation of weight-based dosing of candesartan cilexetil (2-8 mg daily). The dose was doubled after 7 days of therapy if inadequate antihypertensive response was determined by clinic-measured casual BP monitoring (CBPM) and home BP monitoring (HBPM). Three methods of BP measurement were compared before and after 2 weeks of treatment with the final dose of candesartan cilexetil: CBPM, HBPM, and 24-hour continuous ambulatory BP monitoring (ABPM). Self-reported adverse effects and clinical laboratory analyses were used to determine tolerability. RESULTS: Eleven patients (mean age 14.2 y) received a final candesartan cilexetil median daily dose of 8 mg (0.13 mg/kg, range 2-16 mg). Study treatment resulted in significant reductions in systolic and diastolic BP as measured by CBPM (-7.4%, p = 0.03 and -5.9%, p = 0.01, respectively) and by ABPM (-6.0%, p = 0.03 and -10.8%, p = 0.006, respectively), but no significant reductions as measured by HBPM. No clinically significant changes in laboratory measures were observed, and patients reported nonspecific mild adverse effects. CONCLUSIONS: Candesartan cilexetil effectively reduced BP as demonstrated by CBPM and ABPM measurements and was well tolerated in this group of hypertensive children.

In This Issue

In This Issue Clinical Pharmacology & Therapeutics 84, 285 (September 2008). doi:10.1038/clpt.2008.162

Is This the Drug or Dose for You?: Impact and Consideration of Ethnic Factors in Global Drug Development, Regulatory Review, and Clinical Practice

Is This the Drug or Dose for You?: Impact and Consideration of Ethnic Factors in Global Drug Development, Regulatory Review, and Clinical Practice Clinical Pharmacology & Therapeutics 84, 287 (September 2008). doi:10.1038/clpt.2008.144 Authors: S-M Huang & R Temple

Highlights

Highlights Clinical Pharmacology & Therapeutics 84, 296 (September 2008). doi:10.1038/clpt.2008.163 Author:

ASCPT News

ASCPT News Clinical Pharmacology & Therapeutics 84, 298 (September 2008). doi:10.1038/clpt.2008.164

The Critical Path of Warfarin Dosing: Finding an Optimal Dosing Strategy Using Pharmacogenetics

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Warfarin and Pharmacogenomic Testing: The Case for Restraint

Warfarin and Pharmacogenomic Testing: The Case for Restraint Clinical Pharmacology & Therapeutics 84, 303 (September 2008). doi:10.1038/clpt.2008.131 Author: DA Garcia

Individual Genomes Instead of Race for Personalized Medicine

Individual Genomes Instead of Race for Personalized Medicine Clinical Pharmacology & Therapeutics 84, 306 (September 2008). doi:10.1038/clpt.2008.114 Authors: PC Ng, Q Zhao, S Levy, RL Strausberg & JC Venter

What's Needed for Personalized Therapy in Smoking Cessation

What's Needed for Personalized Therapy in Smoking Cessation Clinical Pharmacology & Therapeutics 84, 309 (September 2008). doi:10.1038/clpt.2008.125 Author: RS Epstein

How European Regulators View Foreign Data in the Approval Process

How European Regulators View Foreign Data in the Approval Process Clinical Pharmacology & Therapeutics 84, 311 (September 2008). doi:10.1038/clpt.2008.84 Authors: A Breckenridge & I Hudson

The Need for Clinical Pharmacology Is Greater Than Ever

The Need for Clinical Pharmacology Is Greater Than Ever Clinical Pharmacology & Therapeutics 84, 313 (September 2008). doi:10.1038/clpt.2008.71 Authors: DJ Goldstein, PK Honig & S Spielberg

Response to “The Need for Clinical Pharmacology Is Greater Than Ever”

Response to “The Need for Clinical Pharmacology Is Greater Than Ever” Clinical Pharmacology & Therapeutics 84, 314 (September 2008). doi:10.1038/clpt.2008.72 Author: MM Reidenberg

Racial Differences in Blood Pressure Response to Angiotensin-Converting Enzyme Inhibitors in Children: A Meta-Analysis

Racial Differences in Blood Pressure Response to Angiotensin-Converting Enzyme Inhibitors in Children: A Meta-Analysis Clinical Pharmacology & Therapeutics 84, 315 (September 2008). doi:10.1038/clpt.2008.113 Authors: JS Li, CM Baker-Smith, PB Smith, V Hasselblad, MD Murphy, RM Califf & DK Benjamin Jr.

Toward Personalized Therapy for Smoking Cessation: A Randomized Placebo-controlled Trial of Bupropion

Toward Personalized Therapy for Smoking Cessation: A Randomized Placebo-controlled Trial of Bupropion Clinical Pharmacology & Therapeutics 84, 320 (September 2008). doi:10.1038/clpt.2008.57 Authors: F Patterson, RA Schnoll, EP Wileyto, A Pinto, LH Epstein, PG Shields, LW Hawk, RF Tyndale, N Benowitz & C Lerman

Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin

Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin Clinical Pharmacology & Therapeutics 84, 326 (September 2008). doi:10.1038/clpt.2008.10 Authors: BF Gage, C Eby, JA Johnson, E Deych, MJ Rieder, PM Ridker, PE Milligan, G Grice, P Lenzini, AE Rettie, CL Aquilante, L Grosso, S Marsh, T Langaee, LE Farnett, D Voora, DL Veenstra, RJ Glynn, A Barrett & HL McLeod

Dosing Algorithms to Predict Warfarin Maintenance Dose in Caucasians and African Americans

Dosing Algorithms to Predict Warfarin Maintenance Dose in Caucasians and African Americans Clinical Pharmacology & Therapeutics 84, 332 (September 2008). doi:10.1038/clpt.2008.101 Authors: H Schelleman, J Chen, Z Chen, J Christie, CW Newcomb, CM Brensinger, M Price, AS Whitehead, C Kealey, CF Thorn, FF Samaha & SE Kimmel

Characteriation of Clinical Data Packages Using Foreign Data in New Drug Applications in Japan

Characteriation of Clinical Data Packages Using Foreign Data in New Drug Applications in Japan Clinical Pharmacology & Therapeutics 84, 340 (September 2008). doi:10.1038/sj.clpt.6100346 Authors: M Tanaka & T Nagata

Pharmacokinetics/Genotype Associations for Major Cytochrome P450 Enzymes in Native and First- and Third-generation Japanese Populations: Comparison With Korean, Chinese, and Caucasian Populations

Pharmacokinetics/Genotype Associations for Major Cytochrome P450 Enzymes in Native and First- and Third-generation Japanese Populations: Comparison With Korean, Chinese, and Caucasian Populations Clinical Pharmacology & Therapeutics 84, 347 (September 2008). doi:10.1038/sj.clpt.6100482 Authors: SP Myrand, K Sekiguchi, MZ Man, X Lin, R-Y Tzeng, C-H Teng, B Hee, M Garrett, H Kikkawa, C-Y Lin, SM Eddy, J Dostalik, J Mount, J Azuma, Y Fujio, I-J Jang, S-G Shin, MR Bleavins, JA Williams, JD Paulauskis & KD Wilner

Development of a Large-Scale De-Identified DNA Biobank to Enable Personalized Medicine

Development of a Large-Scale De-Identified DNA Biobank to Enable Personalized Medicine Clinical Pharmacology & Therapeutics 84, 362 (September 2008). doi:10.1038/clpt.2008.89 Authors: DM Roden, JM Pulley, MA Basford, GR Bernard, EW Clayton, JR Balser & DR Masys

Changes in Enoxaparin Pharmacokinetics During Pregnancy and Implications for Antithrombotic Therapeutic Strategy

Changes in Enoxaparin Pharmacokinetics During Pregnancy and Implications for Antithrombotic Therapeutic Strategy Clinical Pharmacology & Therapeutics 84, 370 (September 2008). doi:10.1038/clpt.2008.73 Authors: C Lebaudy, JS Hulot, Z Amoura, N Costedoat-Chalumeau, R Serreau, A Ankri, J Conard, A Cornet, M Dommergues, JC Piette & P Lechat

Model-Based Approach and Signal Detection Theory to Evaluate the Performance of Recruitment Centers in Clinical Trials With Antidepressant Drugs

Model-Based Approach and Signal Detection Theory to Evaluate the Performance of Recruitment Centers in Clinical Trials With Antidepressant Drugs Clinical Pharmacology & Therapeutics 84, 378 (September 2008). doi:10.1038/clpt.2008.70 Authors: E Merlo-Pich & R Gomeni

Application of Software Design Principles and Debugging Methods to an Analgesia Prescription Reduces Risk of Severe Injury From Medical Use of Opioids

Application of Software Design Principles and Debugging Methods to an Analgesia Prescription Reduces Risk of Severe Injury From Medical Use of Opioids Clinical Pharmacology & Therapeutics 84, 385 (September 2008). doi:10.1038/clpt.2008.24 Authors: SM Belknap, H Moore, SA Lanzotti, PR Yarnold, M Getz, DL Deitrick, A Peterson, J Akeson, T Maurer, RC Soltysik, GA Storm & I Brooks

Pharmacogenetic Pathway Analysis of Irinotecan

Pharmacogenetic Pathway Analysis of Irinotecan Clinical Pharmacology & Therapeutics 84, 393 (September 2008). doi:10.1038/clpt.2008.63 Authors: GL Rosner, JC Panetta, F Innocenti & MJ Ratain

The Effect of Gemfibrozil on Repaglinide Pharmacokinetics Persists for at Least 12 h After the Dose: Evidence for Mechanism-based Inhibition of CYP2C8 In Vivo

The Effect of Gemfibrozil on Repaglinide Pharmacokinetics Persists for at Least 12 h After the Dose: Evidence for Mechanism-based Inhibition of CYP2C8 In Vivo Clinical Pharmacology & Therapeutics 84, 403 (September 2008). doi:10.1038/clpt.2008.34 Authors: A Tornio, M Niemi, M Neuvonen, J Laitila, A Kalliokoski, PJ Neuvonen & JT Backman

Genetic Variation in Drug Transporters in Ethnic Populations

Genetic Variation in Drug Transporters in Ethnic Populations Clinical Pharmacology & Therapeutics 84, 412 (September 2008). doi:10.1038/clpt.2008.98 Authors: CD Cropp, SW Yee & KM Giacomini

The Role of Ethnicity in Variability in Response to Drugs: Focus on Clinical Pharmacology Studies

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Ethics at the Intersection of Pharmacoethnicity

Ethics at the Intersection of Pharmacoethnicity Clinical Pharmacology & Therapeutics 84, 424 (September 2008). doi:10.1038/clpt.2008.126 Author: KT FitzGerald

Finding the Right Research Question: Quality Science Depends on Quality Careers

Finding the Right Research Question: Quality Science Depends on Quality Careers Clinical Pharmacology & Therapeutics 84, 427 (September 2008). doi:10.1038/clpt.2008.134 Authors: DA Flockhart & DR Abernethy

CORRIGENDUM: Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin

CORRIGENDUM: Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin Clinical Pharmacology & Therapeutics 84, 430 (September 2008). doi:10.1038/clpt.2008.112

ERRATUM: Propafenone for the Prevention of Atrial Tachyarrhythmias After Cardiac Surgery: A Randomized, Double-blind Placebo-controlled Trial

ERRATUM: Propafenone for the Prevention of Atrial Tachyarrhythmias After Cardiac Surgery: A Randomized, Double-blind Placebo-controlled Trial Clinical Pharmacology & Therapeutics 84, 430 (September 2008). doi:10.1038/clpt.2008.149

CORRIGENDUM: Editorial

CORRIGENDUM: Editorial Clinical Pharmacology & Therapeutics 84, 430 (September 2008). doi:10.1038/clpt.2008.151