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Watson Pharmaceuticals Receives FDA Approval For Generic PLAN B(R)

Watson Pharmaceuticals, Inc. (NYSE: WPI), a leading specialty pharmaceutical company, today announced that its subsidiary, Watson Laboratories, Inc., has received approval today from the United States Food and Drug Administration on its Abbreviated New Drug Application (ANDA) for levonorgestrel tablets, 0.75 mg, for women seventeen years and younger.

BioCis Pharma Reports Positive Phase IIa Clinical Results In Atopic Dermatitis

BioCis Pharma Ltd., a privately held drug development company with its headquarters in Turku, Finland, announced positive results from its Phase IIa clinical trial of ProtoCure(TM) emulsion cream, the company's novel topical drug for dermatology. This double-blind, placebo-controlled study, conducted in Finland, included 13 patients with mild to moderate atopic dermatitis who applied the ProtoCure emulsion cream to the affected skin areas twice daily for up to four weeks.

ThromboGenics And BioInvent Start Recruitment Of Second 100 Patient Cohort In Phase II DVT Prophylaxis Study With TB-402

ThromboGenics NV (Euronext Brussels: THR) and co-development partner BioInvent International (OMXS: BINV) announce that they have started recruitment of a second cohort of patients for their Phase II trial of TB-402. This follows completion of recruitment of the first cohort of 100 patients ahead of schedule. TB-402 is a novel, long acting anticoagulant that is being developed for the prevention of deep vein thrombosis (DVT) following orthopaedic surgery.

First Ten-Year Follow-Up Shows That Treatment With AVONEX® Leads To Long-Term Benefits In Early Multiple Sclerosis Patients

Biogen Idec (NASDAQ: BIIB) announced data results from the CHAMPIONS (Controlled High-Risk AVONEX® (interferon beta-1a) Multiple Sclerosis (MS) Prevention Study In Ongoing Neurologic Surveillance) study, an open label follow-up to CHAMPS (Controlled High Risk Subjects AVONEX MS Prevention Study). Based on the CHAMPS study, AVONEX was granted approval for use in patients who experienced their first clinical MS episode with MRI findings.

ONGLYZA™ (Saxagliptin) Receives Positive Opinion In Europe For The Treatment Of Type 2 Diabetes

Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN) announced that their marketing authorization application for ONGLYZA™ (saxagliptin) received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for the treatment of type 2 diabetes in adults as add-on therapy with metformin, a thiazolidinedione or a sulphonylurea.

Phase III Study Showed Lucentis Improved Vision In Patients With Branch Retinal Vein Occlusion

Genentech, Inc. announced today that the Phase III study BRAVO showed Lucentis® (ranibizumab injection) improved vision, as measured by the primary endpoint of mean change from baseline in best-corrected visual acuity at six months, in patients with macular edema due to branch retinal vein occlusion. The safety profile of Lucentis was consistent with previous experience and no new adverse events related to Lucentis were observed in the study.

WHO, Wyeth Launch Trial In Africa To Test New River Blindness Drug

The WHO on Wednesday announced plans for a clinical trial to test a new drug that "could halve the treatment period for river blindness [or onchocerciasis], a disease that threatens 100 million people mostly in Africa," AFP/Dow Jones Newswires/CNN Money reports (7/1).

FDA Approves Multaq(R) For Patients With Atrial Fibrillation Or Atrial Flutter

Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced that the U.S. Food and Drug Administration (FDA) has approved Multaq(R) (dronedarone) 400 mg Tablets. Patients with atrial fibrillation (AF) or atrial flutter (AFL) soon will have a new treatment option to help improve current management of their disease. Multaq(R) is the first drug approved in the United States that has shown a clinical benefit to reduce cardiovascular hospitalization in patients with AF/AFL.

Spanish Government Selects Novavax's VLP Technology For Comprehensive Flu Vaccine Solution In Spain

Novavax, Inc. (Nasdaq: NVAX) announced its initial agreement to license its proprietary, recombinant virus-like-particle (VLP) vaccine technology to ROVI Pharmaceuticals (Madrid: ROVI) of Spain.

Current Status Of The Development Programs Of New Indications And Formulations For Aricept(R) For Enhancing Patient Value

Eisai Co., Ltd. (Headquarters: Tokyo, President & CEO: Haruo Naito, "Eisai") and Eisai Corporation of North America (Headquarters: Woodcliff Lake, NJ, Chairman and CEO Hajime Shimizu) are currently focusing on three clinical development programs for the company's major product Aricept(R) (donepezil hydrochloride tablets) to further contribute to patients with Alzheimer's disease. As progress in those programs has been made, Eisai announces the status as follows: 1.

Lixte Biotechnology Holdings' Lead Compound, LB-1.2, Enhances The Effectiveness Of Standard Cancer Chemotherapy In Animal Models

Lixte Biotechnology Holdings (OTC Bulletin Board: LIXT) announced that investigators of the National Institute of Neurological Disorders and Stroke (NINDS) and the National Cancer Institute (NCI), National Institutes of Health and Lixte reported that its novel compound, LB-1.2, enhances the effectiveness of two standard chemotherapy drugs in mouse models of human cancers. This research is being conducted under a Cooperative Research and Development Agreement between NINDS and Lixte.

Acura And King Receive FDA Complete Response Letter Regarding Acurox(R)

Acura Pharmaceuticals, Inc. (Nasdaq: ACUR) and King Pharmaceuticals, Inc. (NYSE: KG) announced today that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter regarding the New Drug Application (NDA) for Acurox (oxycodone HC1, USP and niacin, USP) Tablets CII, an immediate release product intended for the relief of moderate-to-severe pain. The Complete Response Letter raises issues regarding the potential abuse deterrent benefits of Acurox(R).

Questions Linger Over Pharmaceutical Deal Agreement To Cut Costs

"As details emerge of the pharmaceutical industry's agreement to kick in $80 billion to help pay for health care reform, the deal is facing increasing skepticism from inside and outside the health care industry," Politico reports.

Drug Industry Increases Lobbying Efforts And Targets Democrats

The drug industry began ramping up its lobbying efforts in 2003, when Medicare Part D began, and now is targeting Democrats. CQ Politics reports: "The industry is increasingly employing Democratic lobbyists with ties to the Obama administration and congressional leaders such as Sen. Max Baucus, D-Mont., chairman of the Senate Finance Committee.

Potential New Drugs: 970 Million And Still Counting - Journal Of The American Chemical Society

Like astronomers counting stars in the familiar universe of outer space, chemists in Switzerland are reporting the latest results of a survey of chemical space - the so-called chemical universe where tomorrow's miracle drugs may reside. The scientists conclude, based on this phase of the ongoing count, that there are 970 million chemicals suitable for study as new drugs.

Roche To Offer Developing Countries Discounted Tamiflu

The pharmaceutical company Roche on Wednesday announced a program to help ensure developing countries have access to its antiviral Tamiflu, for "the management of a novel influenza strain defined by the WHO as having significant and current pandemic potential," Reuters reports (Egenter, 7/1).

DeCODE-led Megastudy Finds New Genetic Clues To Causes Of Schizophrenia

The largest study of the genetics of schizophrenia ever undertaken has revealed several new common single-letter variants in the sequence of the human genome (SNPs) linked to risk of the disease. The study, by a multinational consortium of scientists led by a team from deCODE genetics (Nasdaq: DCGN), analyzed the genomes of more than 50,000 patients and control participants from fourteen countries. It is published today in the online edition of Nature.

Peregrine Awarded European Patent For Innovative Labeling Technology Featured In New Study In The Journal Of Nuclear Medicine

Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM) today announced that it has been awarded a European patent for a novel device and methods for linking biological agents to labels for diagnostic and therapeutic applications. The technology, which is known as In-Line labeling, was developed for the production of radiolabeled anti-cancer antibodies, but is applicable to other agents as well.

Calixa Therapeutics Announces Initiation Of Phase 2 Clinical Trial Of Its Antibiotic, CXA-101, In Patients With Complicated Urinary Tract Infections

Calixa Therapeutics Inc. today announced the initiation of a Phase 2 clinical trial of CXA-101 in patients with complicated urinary tract infections. CXA-101 is a new broad-spectrum, parenteral cephalosporin antibiotic with excellent in vitro and in vivo activity against Pseudomonas aeruginosa, including drug resistant isolates. Calixa is investigating CXA-101 as a potential treatment for serious bacterial infections in hospitalized patients.

Amira Pharmaceuticals Announces Initial Positive Phase 1 Clinical Data For AM211, A Novel Product Candidate For The Treatment Of Respiratory Diseases

Amira Pharmaceuticals, Inc. announced initial positive data from a Phase 1 clinical study of AM211, the company's oral selective antagonist of the DP2 (also known as CRTH2) receptor. The interim results demonstrate that a sustained pharmacodynamic (PD) effect can be achieved with a single dose of AM211. The pharmacokinetic profile indicates safety multiples as compared to exposures observed in safety species.

PROLOR Biotech Awarded Two U.S. Patents For Its Longer-Acting Human Growth Hormone And Longer-Acting Erythropoietin

PROLOR Biotech, Inc. (OTC Bulletin Board: PBTH), formerly Modigene Inc., announced that the U. S. Patent and Trademark Office (PTO) has issued two new patents for the company's long-acting CTP-enhanced human growth hormone (hGH-CTP) and human erythropoietin (EPO-CTP). The patents cover the composition of PROLOR's proprietary pharmaceutical compounds as well as certain associated methods.

Cephalon Submits NUVIGIL Supplemental New Drug Application For The Treatment Of Excessive Sleepiness Associated With Jet Lag Disorder

Cephalon, Inc. (Nasdaq: CEPH) announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) requesting approval of NUVIGIL(R) (armodafinil) Tablets [C-IV] for the indication of improved wakefulness in patients with excessive sleepiness associated with jet lag disorder resulting from eastbound travel.

Centocor Ortho Biotech Inc. Awarded $1.67 Billion Patent Jury Verdict From Abbott Laboratories

Centocor Ortho Biotech Inc. announced today that a federal jury has returned a verdict of $1.67 billion against Abbott Laboratories in a patent infringement suit. "We are pleased that the jury has ruled in our favor in the patent litigation case against Abbott," said Kim Taylor, President, Centocor Ortho Biotech Inc.

Baxter To Acquire Continuous Renal Replacement Therapy Business From Edwards Lifesciences

Baxter International Inc. (NYSE:BAX) announced today a definitive agreement with Edwards Lifesciences Corporation (NYSE:EW) under which Baxter will acquire certain assets related to Edwards' hemofiltration product line, also known as Continuous Renal Replacement Therapy (CRRT). The transaction is expected to close in the third quarter of 2009, pending regulatory approvals.

Vietnamese Drug Authority Teams With United States Standards-Setting Organization

As Vietnam's industrial capabilities have developed rapidly in recent decades, government officials have recognized the importance of helping to secure the nation's supply of medicines. In an important milestone addressing this need, the Vietnamese Pharmacopoeia Commission (VPC) has signed a memorandum of understanding (MOU) with the U.S. Pharmacopeial (USP) Convention.

Prevalence of Sodium Bicarbonate-Induced Alkalemia in Cardiopulmonary Arrest Patients(July/August)

BACKGROUND: Intravenous sodium bicarbonate (SB) administration during cardiopulmonary arrest (CPA) is intended to counteract lactic acidosis due to hypoxia, poor perfusion, and anaerobic metabolism. Despite a lack of documented efficacy and a level III recommendation from the American Heart Association, SB is widely used during resuscitation events. SB has both theoretical and measurable adverse effects. Excess or poorly timed administration during a CPA may elevate a patient's pH, inducing alkalemia. Despite decades of controversy surrounding use of this drug, the prevalence of SB-induced alkalemia has not been previously documented. OBJECTIVE: To estimate the prevalence of SB-induced alkalemia in inpatients after CPA and to investigate the pattern of SB administration. METHODS: Medical records were retrospectively reviewed with attention to SB administration and arterial blood gas (ABG) data. After application of inclusion and exclusion criteria to 264 CPA patients, the study group comprised 88 patients. When measured, if PCO2 and pH were above normal limits after SB administration, we concluded that SB contributed to the alkalemia. RESULTS: Twenty-seven (31%) patients received SB without any ABG data, and 70 (79%) patients received at least one empiric SB dose. Of the 61 patients with ABG data, alkalemia occurred in 10, a prevalence of 16%. Administration of SB increased pH in only 9 (15%) other CPA patients and had no effect in the 42 (69%) remaining patients. CONCLUSIONS: Administration of SB during CPA was causally linked with inducing alkalemia in 16% of patients. Early collection of ABG samples may assist in optimizing pH during CPA and thus reduce unwarranted empiric use of SB.

Use of {beta}-Blockers in Patients with an Implantable Cardioverter Defibrillator(July/August)

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are indicated for both primary and secondary prevention of sudden cardiac arrest. β-Blockers are also indicated in most patients who have an indication for an ICD; however, their use in this population is not well described. Some clinicians may be unaware of the recommendation for β-Blockers in this population. OBJECTIVE: To explore β-blocker use among ICD recipients. METHODS: Adults who received their first ICD at Duke Hospital between July 1999 and July 2004 for primary or secondary prevention of sudden cardiac arrest were identified. Using hospital data, β-blocker use was determined at time of discharge, and characteristics of users were compared with those of nonusers. Continued use of β-blockers after ICD implant was explored in the subset of patients included in the Duke Databank for Cardiovascular Disease (DDCD). RESULTS: The study cohort comprised 804 patients, 652 (81%) with ICD for secondary prevention of sudden cardiac arrest and 152 (19%) for primary prevention. The median age was 65 years and 75% of the patients were men. A total of 544 (68%) received a β-blocker at time of ICD implant. There were no substantial changes in the proportion of patients with β-blocker use from 1999 through 2004, overall or within the primary or secondary prevention groups. However, β-blocker use was higher in the secondary prevention group than in the primary prevention group (69% vs 60%; p = 0.02). A higher proportion of β-blocker users versus nonusers had ischemic heart disease (82% vs 68%; p < 0.0001), heart failure (84% vs 71%; p < 0.0001), previous myocardial infraction (51% vs 44%; p = 0.05), and ventricular arrhythmias (82% vs 76%; p = 0.04). Of the 425 patients included in the DDCD, only 241 (57%) were receiving β-blockers at time of implant and during clinical follow-up. CONCLUSIONS: Lower than optimal use of β-blockers suggests the need for new methods of including evidence-based medications in clinical practice, especially for complex patients for whom numerous clinical practice guidelines may apply.

Sertraline-Induced Rhabdomyolysis in an Elderly Patient with Dementia and Comorbidities (July/August)

OBJECTIVE: To describe a case of sertraline-induced rhabdomyolysis in an elderly patient with dementia and comorbidities. CASE SUMMARY: A 71-year-old woman visited a psychiatrist in September 2007 for her depressed mood. Her medical history included vascular dementia accompanied by depression, arterial hypertension, and heart failure, as well as cardiac pacemaker implantation several years earlier for severe bradyarrythmia. She had begun taking amisulpride 50 mg/day and diazepam 2 mg at bedtime 6 months prior to the psychiatrist appointment, with poor relief of her depressed mood. Her drug therapy also included nicergoline 30 mg/day, amlodipine 5 mg/day, aspirin 100 mg/day, candesartan 16 mg/day, and atenolol 25 mg/day. At this psychiatrist visit, sertraline 50 mg/day was added for her depression, and was continued after a geriatrician visit in October. Her mood improved significantly. On December 18, 2007, she was admitted to the cardiology unit to undergo a pacemaker replacement. Laboratory tests revealed creatine kinase (CK) 7952 IU/L, lactate dehydrogenase 1021 IU/L, myoglobin 2322 U/L, and aspartate aminotransferase 362 IU/L, resulting in a diagnosis of iatrogenic rhabdomyolysis. Amisulpride and sertraline were discontinued. On December 24, serum CK was 839 IU/L and myoglobin was 91 U/L and the patient was discharged. On January 22, laboratory tests showed normal values of CK, CK-MB, and myoglobin. Sertraline 50 mg/day was again prescribed for the patient's persistent depressed mood. Fifteen days later, blood tests showed CK 1327 IU/L and myoglobin 324 U/L; therefore, the drug was discontinued. CK and myoglobin levels normalized a week later. On April 2, escitalopram was started. At time of writing, there was no evidence of any increase in CK, myoglobin, or other markers of rhabdomyolysis. DISCUSSION: The Naranjo probability scale indicated a probable relationship between sertraline treatment and the onset of rhabdomyolysis. No relationship between amisulpride and rhabdomyolysis was found. Furthermore, rechallenge with sertraline caused CK and myoglobin to again increase, which was reversed following a discontinuation of sertraline. The patient's other comorbidities and medications have not been suggested as possible interactions with sertraline that can cause rhabdomyolysis. Genetic defects of sertraline demethylation and/or P-glycoprotein binding or concurrent circumstances may explain the onset of rhabdomyolysis in this particular patient. CONCLUSIONS: This patient's rhabdomyolysis was probably induced by sertraline therapy.

Impact of Nicotine Replacement Therapy on Postoperative Mortality Following Coronary Artery Bypass Graft Surgery(July/August)

BACKGROUND: Nicotine replacement therapy (NRT) has recently been associated with increased mortality in patients in medical intensive care units (ICUs). Although NRT is frequently used in cardiothoracic surgery patients, no safety data exist for use in this population. OBJECTIVE: To ascertain the impact of NRT on in-hospital mortality following coronary artery bypass graft (CABG) surgery. METHODS: This was a retrospective matched cohort pilot study in a 22-bed cardiothoracic surgery ICU. Patients prescribed transdermal NRT after CABG were randomly selected and matched to current smokers not prescribed NRT according to Acute Physiology and Chronic Health Evaluation II scores (N = 134). Data on comorbid conditions and pack-year history were also obtained. To compare these patients with nonsmoking patients, a larger unmatched population was also evaluated. The total number of patients prescribed NRT, current smokers not prescribed NRT, and nonsmokers who were evaluated in our study was 2057. RESULTS: Sixty-seven NRT patients were well matched with 67 current smokers in terms of baseline demographics and procedures. Mortality was nonsignificantly higher in the NRT group versus the non-NRT smoker group (4.5% vs 0.0%; p = 0.080). In an evaluation of a larger population controlled for differences in baseline characteristics, an increase in mortality due to NRT was found (OR 6.06; 95% CI 1.65 to 22.21). In an a priori subgroup of the overall population, mortality was significantly higher in patients receiving NRT after off-pump CABG versus smokers not receiving NRT (OR 6.49; 95% CI 1.29 to 32.56). CONCLUSIONS: The use of NRT in a postoperative CABG surgery population resulted in a significant increase in mortality when adjusted for baseline characteristics. Patients receiving NRT after off-pump cardiac surgery may be particularly susceptible. Additional evaluation in large patient cohorts with prospective controls is warranted.

Pediatric Medication Education Text, 5th edition (July/August)

Pharmacology and Therapeutics: Principles to Practice (July/August)

Travel Medicine, 2nd Edition (July/August)

Effect of a Warfarin Adherence Aid on Anticoagulation Control in an Inner-City Anticoagulation Clinic Population(July/August)

BACKGROUND: Poor adherence to warfarin therapy is a major contributor to subtherapeutic anticoagulation. OBJECTIVE: To determine whether use of a monthly medication organizer, filled at each clinic visit, improves anticoagulation control among warfarin-treated patients. METHODS: Patients who had a history of nonadherence to warfarin and were attending an inner-city anticoagulation clinic were enrolled in this prospective cohort study and provided with a 28-day medication organizer. Patients were instructed to bring their organizers and warfarin tablets to each anticoagulation clinic visit over the following 3 months. At each visit, the international normalized ratio (INR) was measured, warfarin adherence was assessed, and the organizer was filled with the prescribed warfarin regimen until the next scheduled visit. Data on warfarin adherence and INR values during the 3 months prior to enrollment were collected from medical records and compared with postenrollment data. RESULTS: Thirteen patients were enrolled and completed at least one postenrollment clinic visit. Adherence to warfarin therapy improved with use of the medication organizer (mean ± SD preenrollment 55 ± 25%, postenrollment 67 ± 21%; p = 0.06). There was a significant decrease in the proportion of subtherapeutic INR values (60 ± 25% to 35 ± 29%; p = 0.04) and a significant improvement in the percent of time spent within the therapeutic INR range (32 ± 22% to 56 ± 28%; p = 0.03) after enrollment. CONCLUSIONS: Use of a monthly medication organizer significantly reduced the percent of subtherapeutic INR values and improved the time spent within the therapeutic anticoagulation range among previously nonadherent patients managed in an inner-city anticoagulation clinic.

Tarascon Pocket Pharmacopoeia: 2009 Deluxe Lab-Coat Pocket Edition, 10th Edition (July/August)

Evidence-Based Emergency Medicine (July/August)

Pharmacy: An Introduction to the Profession, 2nd Edition (July/August)

Delirium in a Patient with Toxic Flecainide Plasma Concentrations: The Role of a Pharmacokinetic Drug Interaction with Paroxetine (July/August)

OBJECTIVE: To describe a case of flecainide-induced delirium associated with a pharmacokinetic drug interaction with paroxetine. CASE SUMMARY: A 69-year-old white female presented to the emergency department with a history of confusion and paranoia over the past several days. On admission the patient was taking carvedilol 12 mg twice daily, warfarin 2 mg/day, folic acid 1 mg/day, levothyroxine 100 µg/day, pantoprazole 40 mg/day, paroxetine 40 mg/day, and flecainide 100 mg twice daily. Flecainide had been started 2 weeks prior for atrial fibrillation. Laboratory test findings on admission were notable only for a flecainide plasma concentration of 1360 µg/L (reference range 200-1000). A metabolic drug interaction between flecainide and paroxetine, which the patient had been taking for more than 5 years, was considered. Paroxetine was discontinued and the dose of flecainide was reduced to 50 mg twice daily. Her delirium resolved 3 days later. DISCUSSION: Flecainide and pharmacologically similar agents that interact with sodium channels may cause delirium in susceptible patients. A MEDLINE search (1966-January 2009) revealed one in vivo pharmacokinetic study on the interaction between flecainide, a CYP2D6 substrate, and paroxetine, a CYP2D6 inhibitor, as well as 3 case reports of flecainide-induced delirium. According to the Naranjo probability scale, flecainide was the probable cause of the patient's delirium; the Horn Drug Interaction Probability Scale indicates a possible pharmacokinetic drug interaction between flecainide and paroxetine. CONCLUSIONS: Supratherapeutic flecainide plasma concentrations may cause delirium. Because toxicity may occur when flecainide is prescribed with paroxetine and other potent CYP2D6 inhibitors, flecainide plasma concentrations should be monitored closely with commencement of CYP2D6 inhibitors.

Probable Interaction Between Warfarin and Marijuana Smoking (July/August)

OBJECTIVE: To report a probable interaction between warfarin and marijuana smoking, resulting in increased international normalized ratio (INR) values and bleeding complications. CASE SUMMARY: A 56-year-old white male had been receiving chronic warfarin therapy for 11 years after mechanical heart valve replacement. He was admitted to the hospital with a diagnosis of upper gastrointestinal bleeding. Upon admission, his INR value was supratherapeutic at 10.41, and his hemoglobin level was 6.6 g/dL. He received 4 units of fresh frozen plasma and one 10-mg dose of oral vitamin K; his INR was 1.8 the next day. He was discharged 7 days after admission. Fifteen days after hospital discharge, he was readmitted with a constant nosebleed and increased bruising. His INR value was 11.55. After treatment, he was discharged with an INR value of 1.14. The patient smoked marijuana more frequently throughout the period of these 2 hospitalizations due to his depression. He was counseled by the pharmacist on the potential interaction of warfarin and marijuana. The patient decided to stop smoking marijuana after the third counseling session. During the 9 months that he did not smoke marijuana, his INR values ranged from 1.08 to 4.40 with no significant bleeding complications. DISCUSSION: Marijuana may increase warfarin anticoagulant effect by inhibiting its metabolism, and to a lesser extent, displacing warfarin from protein-binding sites. Other causes (eg, nonadherence) of the patient's increased INR were ruled out. Using the Horn Drug Interaction Probability Scale, our patient's warfarin- marijuana interaction appeared to be probable. CONCLUSIONS: To our knowledge, there have been no other reported cases of warfarin-marijuana interaction. While more clinical reports would be useful to confirm this interaction, clinicians should be aware of its probability so as to manage patients appropriately.

Outcomes of Perioperative {beta}-Blockade in Patients Undergoing Noncardiac Surgery: A Meta-Analysis(July/August)

BACKGROUND: Several studies have evaluated the impact on myocardial infarction (MI), stroke, and overall mortality of perioperative β-blocker use in patients undergoing noncardiac surgery (NCS). However, most studies did not have adequate sample size and statistical power and were therefore underpowered to adequately evaluate these endpoints. OBJECTIVE: To conduct a meta-analysis to determine the balance of benefits and harms associated with perioperative β-blocker use in NCS. METHODS: A systematic literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted from January 1960 through February 2009. Manual reference search was performed to identify additional relevant trials. Randomized, double-blinded, placebo-controlled trials comparing the use of β-blockers with placebo; using β-blockers perioperatively in β-blocker-naïve patients undergoing NCS; and evaluating endpoints of MI, stroke, or all-cause mortality were included. RESULTS: Six trials (N = 10,183) met our inclusion criteria. Perioperative β-blocker use was associated with a significant reduction in patients' odds of developing MI (OR 0.74, 95% CI 0.61 to 0.89) but a significant increase in odds of developing stroke (OR 1.98, 95% CI 1.23 to 3.20) and also a non-significant increase in mortality (OR 1.21, 95% CI 0.98 to 1.49) versus placebo. Control-rate meta-regression determined that patients with highest baseline odds of stroke had decreased relative odds of having a stroke with a β-blocker versus placebo (β coefficient -0.97; 95% credible interval -1.04 to -0.90). CONCLUSIONS: When perioperative β-blockers are used in NCS patients, there is a trade-off between reduction in MI and increase in stroke, with a troubling trend toward an increase in mortality. Patients with lower baseline odds of developing stroke appear to be at greater risk of β-blocker-induced stroke.

Authors' Reply (July/August)

Assessing the Clinical Efficacy of Sildenafil for the Treatment of Female Sexual Dysfunction(July/August)

OBJECTIVE: To review the clinical data regarding the efficacy and safety of sildenafil for the treatment of female sexual dysfunction (FSD). DATA SOURCES: A MEDLINE search from 1950 to February 2009 was conducted using the key words sildenafil and female sexual dysfunction. Human studies and publication in English were used as primary limits. A combination of several publication-type limits was used to locate the clinical trials (eg, clinical trial, controlled clinical trial, randomized clinical trial). A bibliographic search was also performed of all located articles. STUDY SELECTION AND DATA EXTRACTION: Clinical trials involving sildenafil treatment of premenopausal and postmenopausal women with FSD and women with FSD due to concomitant medications and/or disease states were reviewed. DATA SYNTHESIS: An increasing number of clinical trials have been published regarding the treatment of FSD with sildenafil. Eight studies demonstrated a possible benefit from treatment for FSD in patients receiving sildenafil, regardless of dose, while 4 trials did not show any significant differences with treatment. It appears that sildenafil might be beneficial for women with FSD caused by diseases such as multiple sclerosis, type 1 diabetes, spinal cord injury, and use of antidepressant medications. CONCLUSIONS: Although data suggest a possible role of sildenafil for the treatment of FSD, the information should be interpreted cautiously, as many of the studies included small sample sizes, used inappropriate statistical tests, and used nonvalidated assessment tools. A better FSD classification system and consistent use of validated assessment tools might help alleviate differences among clinical trials and provide a more cohesive foundation for assessing the safety and efficacy of sildenafil for the treatment of FSD.

Comment: Terlipressin for Children with Extremely Low Cardiac Output After Open Heart Surgery (July/August)

Drug-Drug Interaction Between Clopidogrel and the Proton Pump Inhibitors (July/August)(CE)

OBJECTIVE: To evaluate the interaction between clopidogrel and proton pump inhibitors (PPIs). DATA SOURCES: Literature retrieval was accessed through PubMed (1980- January 2009), abstracts from 2008 American Heart Association and 2009 Society of Cardiovascular Angiography and Interventions Scientific Sessions, and media press releases using the terms clopidogrel, proton pump inhibitors, cytochrome 2C19, genetic cytochrome P450 polymorphisms, and drug interaction. In addition, reference citations from publications identified in the search were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant original research articles and review articles were evaluated. Articles were selected if they were published in English and focused on any of the key words or appeared to have substantial content addressing the drug interaction. DATA SYNTHESIS: Recent attention has been placed on a potential interaction observed between clopidogrel and the widely used PPIs. Preliminary evidence suggests that omeprazole interacts with clopidogrel, reducing clopidogrel's antiplatelet effects as measured by various laboratory tests. Most data indicate that the interaction involves the competitive inhibition of the CYP2C19 isoenzyme. The interaction appears to be clinically significant, as several retrospective analyses have shown an increase in adverse cardiovascular outcomes when PPIs and clopidogrel are used concomitantly. However, this may not be a class effect. CONCLUSIONS: Available data suggest that omeprazole is the PPI most likely to have a significant interaction with clopidogrel. Further studies are needed to determine that an interaction between the other PPIs and clopidogrel does not exist. In situations in which both clopidogrel and a PPI are indicated, pantoprazole should be used since it is the PPI least likely to interact with clopidogrel.

In This Issue

In This Issue Clinical Pharmacology & Therapeutics 86, 1 (July 2009). doi:10.1038/clpt.2009.96

Biomarkers: Principles, Policies, and Practice

Biomarkers: Principles, Policies, and Practice Clinical Pharmacology & Therapeutics 86, 3 (July 2009). doi:10.1038/clpt.2009.77 Author: JA Wagner

Highlights

Highlights Clinical Pharmacology & Therapeutics 86, 8 (July 2009). doi:10.1038/clpt.2009.91 Author:

ASCPT News

ASCPT News Clinical Pharmacology & Therapeutics 86, 10 (July 2009). doi:10.1038/clpt.2009.84

Chutes and Ladders on the Critical Path:Comparative Effectiveness, Product Value, and the Use of Biomarkers in Drug Development

Chutes and Ladders on the Critical Path:Comparative Effectiveness, Product Value, and the Use of Biomarkers in Drug Development Clinical Pharmacology & Therapeutics 86, 12 (July 2009). doi:10.1038/clpt.2009.33 Author: J Woodcock

Direct-to-Consumer Genetic Testing: Failure Is Not an Option

Direct-to-Consumer Genetic Testing: Failure Is Not an Option Clinical Pharmacology & Therapeutics 86, 15 (July 2009). doi:10.1038/clpt.2009.63 Author: RB Altman

Direct-to-Consumer Genetic Testing: The Need to Get Retail Genomics Right

Direct-to-Consumer Genetic Testing: The Need to Get Retail Genomics Right Clinical Pharmacology & Therapeutics 86, 17 (July 2009). doi:10.1038/clpt.2009.56 Authors: AD Schickedanz & RC Herdman

Personalized Medicine: A Perk of Privilege?

Personalized Medicine: A Perk of Privilege? Clinical Pharmacology & Therapeutics 86, 21 (July 2009). doi:10.1038/clpt.2009.75 Author: JJ Griggs

Educating for Personalized Medicine: A Perspective From Oncology

Educating for Personalized Medicine: A Perspective From Oncology Clinical Pharmacology & Therapeutics 86, 23 (July 2009). doi:10.1038/clpt.2009.76 Authors: DR Parkinson & J Ziegler

Biomarkers in Clinical Drug Development

Biomarkers in Clinical Drug Development Clinical Pharmacology & Therapeutics 86, 26 (July 2009). doi:10.1038/clpt.2009.57 Author: JVS Gobburu

Addressing the Challenges of the Clinical Application of Pharmacogenetic Testing

Addressing the Challenges of the Clinical Application of Pharmacogenetic Testing Clinical Pharmacology & Therapeutics 86, 28 (July 2009). doi:10.1038/clpt.2009.30 Authors: ON Ikediobi, J Shin, RL Nussbaum & KA Phillips

The Value, Qualification, and Regulatory Use of Surrogate End Points in Drug Development

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