Pharmacology RSS : Gourt

Electric Field Propels Worms To Test New Drugs

A Nobel-winning process for testing new drugs to treat diseases such as Huntington's, Parkinson's, and muscular dystrophy is getting an electrical charge. Researchers at McMaster University have developed a way to propel and direct microscopic-sized worms (C. elegans nematodes) along a narrow channel using a mild electric field...

New Analysis Showed Effient(R) Cost-Effective Compared With Clopidogrel For Patients With Acute Coronary Syndromes Undergoing PCI

Results from a health economic substudy of the TRITON-TIMI 38 clinical trial showed that among patients with acute coronary syndromes (ACS) managed with percutaneous coronary intervention (PCI), including stenting, treatment with Effient(®) (prasugrel) compared with branded clopidogrel (Plavix(®)) was more cost effective, and in most cases cost saving...

Quark Pharmaceuticals Poised To Advance Clinical Studies Of QPI 1002

Quark Pharmaceuticals, Inc., the world leader in clinical development of RNAi-based therapeutics, announced that the independent Data Safety Monitoring Board ("DSMB") recommended that QPI-1002 (I5NP) continue on to the next phase of clinical testing...

Intellikine Initiates Phase I Clinical Trial For Targeted Anticancer Drug INK128

Intellikine, Inc. has initiated a Phase I clinical trial for its targeted anticancer drug INK128, a novel orally-available small molecule inhibitor of both the TORC1 and TORC2 complexes, key components of the PI3K/mTOR signaling pathway. "Advancing INK128 to this point is a significant achievement for Intellikine," said Troy Wilson, Ph.D., J.D., President and CEO of Intellikine...

Excaliard Initiates Phase 2 Trials In U.S. For Its Skin Scarring Drug, EXC 001

Excaliard Pharmaceuticals, Inc. announced the initiation of three proof of concept Phase 2 trials of EXC 001, an antisense medicine that reduces fibrosis, for the amelioration of skin scarring and other fibrotic disorders. The U.S...

Icon Bioscience Initiates Phase 2/3 Pivotal Clinical Study Of Novel Ophthalmic Drug Candidate

Icon Bioscience, Inc., (IBI), a privately held biopharmaceutical company that specializes in the development and commercialization of novel ophthalmic pharmaceuticals announced that it has initiated its Phase 2/3 pivotal clinical trial to assess the safety and efficacy of IBI-10090 in patients undergoing cataract surgery...

Dainippon Sumitomo Pharma America Announces The NDA Submission Of Lurasidone To The FDA For The Treatment Of Schizophrenia

Dainippon Sumitomo Pharma America, Inc. (DSPA), a U.S. subsidiary of Dainippon Sumitomo Pharma Co., Ltd. (DSP), submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for lurasidone, an investigational atypical antipsychotic agent for the treatment of schizophrenia...

EnVivo Enters Phase 2b Trials For Its EVP-6124 Compound In The Treatment Of Schizophrenia

EnVivo Pharmaceuticals announced the initiation and dosing of patients in a Phase 2b study of its EVP-6124 compound, a selective alpha-7 nicotinic agonist in patients with schizophrenia. EnVivo is conducting the multi-center, dose ranging, placebo controlled, three-month study in the U.S. and Europe...

Alternative Swine Flu Vaccination Provided By Insect Cells

Scientists in Vienna have developed a new technique for producing vaccines for H1N1, 'swine flu', based on insect cells. The research, published in the Biotechnology Journal, reveals how influenza vaccines can be produced faster than through the traditional method of egg-based production, revealing a new strategy for the fight against influenza pandemics...

The High Price Of FDA Approval

The Food and Drug Administration is trying to get some unapproved drugs off the market, Kaiser Health News reports in a story produced in partnership with the Philadelphia Inquirer. But sometimes the brand-name replacement is much more expensive (Meyer, 12/29). Read full story. This information was reprinted from kaiserhealthnews.org with kind permission from the Henry J...

FDA Grants Priority Review Of Pirfenidone NDA For The Treatment Of Patients With IPF

InterMune, Inc. (Nasdaq: ITMN) announced that the U.S. Food and Drug Administration (FDA) has accepted for review and granted Priority Review designation for the company's New Drug Application (NDA) for pirfenidone for the treatment of patients with idiopathic pulmonary fibrosis (IPF)...

Emerald BioStructures Publication In Nature Biotechnology Details Discovery Of Allosteric Small Molecule Modulators Of PDE4 With Reduced Side Effects

Emerald BioStructures (formerly deCODE biostructures) announced today a publication in the December 27, 2009 advance online issue of Nature Biotechnology, detailing the application of structure-based drug design (SBDD) to engineer new allosteric small molecule modulators of the enzyme phosphodiesterase-4 (PDE4), with reduced side effects...

Muscular Dystrophy Therapy Based On Tarantula-Venom To Be Advanced By UB Scientists' Biotech Company

University at Buffalo biophysicists have found a protein in tarantula venom that shows promise as a potential therapy for muscular dystrophy (MD). They have formed a start-up biotech company in Buffalo -- Rose Pharmaceuticals -- to advance the drug to clinical trials...

D-Pharm (TASE: DPRM) Announces Enrollment Of First Patient In DP-b99 Phase III Efficacy Study, MACSI

D-Pharm Ltd (TASE: DPRM) announced enrollment of patients with acute ischemic stroke into its Phase III clinical study of DP-b99 (MACSI). The first patient has been enrolled at the Wolfson Medical Center, Israel. The MACSI trial involves numerous medical centers in the US, Canada, Europe, Israel, South Africa, South Korea and Brazil...

Bionovo Announces Publication Describing First Novel Dual MTOR Inhibitor, BN107, For The Treatment Of Breast Cancer

Bionovo, Inc. (Nasdaq: BNVI) announced the publication of results from its study on the anti-tumor mechanism of BN107. The results of the study, published in the International Journal of Cancer, describe the potential molecular mechanisms mediating the selective pro-apoptotic (cell death) effect induced by BN107 on estrogen receptor negative (ER-) breast cancer cells...

Arena Pharmaceuticals Announces Merck Discontinues Development Of Investigational Niacin Receptor Agonist Program For Atherosclerosis

Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced Merck and Co., Inc.'s decision (through an affiliate) to discontinue development of MK-1903, an investigational niacin receptor agonist to treat atherosclerosis being developed under its research collaboration with Arena. Merck also informed Arena that the company will not continue the collaboration...

Sinovac Files Clinical Trial Application With SFDA For Vaccine Against Hand, Foot, And Mouth Disease

Sinovac Biotech Ltd. ( SVA), a leading provider of biopharmaceutical products in China, announced that it has filed the application with China's State Food and Drug Administration (SFDA) to commence a human clinical trial for its vaccine against human enterovirus 71 (EV 71), which causes hand, foot, and mouth disease (HFMD)...

Soligenix Announces Publication Of Positive Pre Clinical Results With RiVax(TM), Its Vaccine Against Ricin Toxin

Soligenix, Inc. (OTC Bulletin Board: SNGX) (Soligenix or the Company), formerly known as DOR BioPharma, Inc., a late-stage biotechnology company, announced the publication of an article in the January 2010 edition of Infection and Immunity, detailing the characteristics of several immunodominant regions of ricin A chain, the antigenic component of RiVax((TM))...

Alimera Announces Positive Results From The Two Phase 3 FAME(TM) Trials Of Iluvien(R) In Patients With Diabetic Macular Edema

Alimera Sciences, Inc., a privately held biopharmaceutical company that specializes in the research, development and commercialization of prescription ophthalmic pharmaceuticals, reported top-line results from the month 24 readout of the FAME Study...

GenWay's CLIA-certified And California-licensed Laboratory Is Granted CAP Accreditation

GenWay Biotech, Inc. GenWay Clinical Laboratory, San Diego, California, has been awarded an accreditation by the College of American Pathologists (CAP), based on results of a recent onsite inspection. The laboratory's director was advised of this national recognition and congratulated for the "excellence of the services being provided." GenWay Biotech Inc...

Former CDC Head To Lead Merck's Vaccine Division

The pharmaceutical company Merck on Monday named former CDC head Julie Gerberding as president of the company's vaccine division, Reuters reports...

Results From Phase II Trial In Critical Care Medicine Showed Eritoran Tetrasodium (E5564) To Be Well Tolerated In Patients With Severe Sepsis

The investigational compound, eritoran tetrasodium ("eritoran," also known as E5564) appeared to be well tolerated in patients with severe sepsis in a Phase II trial published in the January issue of Critical Care Medicine, the official journal of the Society of Critical Care Medicine, the largest multiprofessional organization dedicated to ensuring excellence and consistency i...

Arena Pharmaceuticals Submits New Drug Application To FDA For Lorcaserin For Weight Management

Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced that it has submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for lorcaserin, Arena's internally discovered and developed drug candidate for weight management, including weight loss and maintenance of weight loss...

Mylan Receives Tentative FDA Approval Under PEPFAR For Matrix Laboratories' New Drug Application (NDA) For Efavirenz Tablets

Mylan Inc. (Nasdaq: MYL) announced that its subsidiary Matrix Laboratories Limited has received tentative approval from the U.S. Food and Drug Administration (FDA) under the President's Emergency Plan for AIDS Relief (PEPFAR) for its New Drug Application (NDA) for Efavirenz Tablets, 50 mg, 100 mg and 200 mg...

Cephalon Provides Update On Regulatory Review Of NUVIGIL For The Treatment Of Excessive Sleepiness Associated With Jet Lag Disorder

Cephalon, Inc. (Nasdaq: CEPH) announced that the U.S. Food and Drug Administration (FDA) has extended the action date to March 29, 2010, for its review of the supplemental New Drug Application (sNDA) for NUVIGIL® (armodafinil) Tablets [C-IV]. The sNDA is for the indication of improved wakefulness in patients with excessive sleepiness associated with jet lag disorder due to eastbound travel...

Bronchial Fistula Associated with Sunitinib in a Patient Previously Treated with Radiation Therapy (February)

OBJECTIVE: To report a case of bronchial fistula associated with sunitinib in a patient previously treated with radiation therapy. CASE SUMMARY: A 40-year-old man with renal cell cancer diagnosed in 2005 and initially treated by radical nephrectomy presented in March 2007 with a recurrence with cerebral, mediastinal, and lung metastases. A thoracic computed tomography (CT) scan showed a subcarinal tumor obstructing the bronchus intermedius. The patient was initially treated with cerebral and thoracic radiotherapy and then with sunitinib 50 mg/day (4 weeks on, 2 weeks off). Two months after the beginning of treatment, a CT scan revealed a dramatic reduction in the size of the tumor, associated with a bronchial fistula. This was confirmed by flexible bronchoscopy, which showed complete necrosis of the tumor and a large perforation of the bronchus intermedius. Sunitinib was immediately withdrawn and antibiotic prophylaxis was instituted. It was not possible to place an endobronchial stent. Two weeks later, flexible bronchoscopy revealed the reappearance of a yellowish mass protruding into the bronchus intermedius (40% obstruction). A few months later, the obstruction of the bronchus intermedius progressed to 90% and was associated with a contralateral obstruction of the left mainstem bronchus (20%). A rigid bronchoscopy was then performed to clear the obstruction and an endobronchial stent was placed, with satisfactory initial results. In February 2008, the patient presented with new bronchial obstruction under the endobronchial stent but refused a rigid bronchoscopy and died in March 2008. DISCUSSION: Sunitinib, a multitarget tyrosine kinase inhibitor with antiangiogenic and antitumoral activities, has been approved for the treatment of advanced renal cell carcinoma. This treatment is generally well tolerated. Serious complications may occur, however. According to the Naranjo probability scale, the bronchial fistula was possibly related to sunitinib treatment. CONCLUSIONS: This is a rare case of a bronchial perforation leading to a fistula associated with sunitinib treatment after mediastinal radiation therapy. Clinicians may consider strict follow-up of patients with proximal lung metastases treated with sunitinib (CT scan and, if appropriate, placement of an endobronchial stent).

Safety of Subcutaneous Octreotide in Patients with Sulfonylurea-Induced Hypoglycemia and Congestive Heart Failure (February)

OBJECTIVE: To report the safe use of subcutaneous octreotide in the treatment of sulfonylurea-induced hypoglycemia in 2 patients with severe congestive heart failure. CASE SUMMARY: Two patients with congestive heart failure with systolic dysfunction presented with severe hypoglycemia (blood glucose level: patient 1, 31 mg/dL; patient 2, 36 mg/dL) secondary to sulfonylurea agents. The mechanism of hypoglycemia was poor oral intake and prolonged half-life of the drugs due to renal failure. Hypoglycemia was refractory to glucose supplementation. Patient 1 received 2 doses of octreotide 50 µg subcutaneously 12 hours apart, with resolution of hypoglycemia (blood glucose level: <33 mg/dL before administration of octreotide, 62 mg/dL after first dose, 121 mg/dL after second dose). Patient 2 received an initial dose of octreotide 25 µg subcutaneously; hypoglycemia persisted after this dose, and the patient was given 2 doses of 50 µg subcutaneously 12 hours apart, leading to resolution of hypoglycemia (blood glucose level: 57 mg/dL before administration of octreotide, 80 mg/dL after first dose, 85 mg/dL after second dose, 146 mg/dL after third dose). Resolution of hypoglycemia with octreotide treatment obviated the need for prolonged intravenous dextrose infusions. No local or systemic adverse effects, especially cardiac adverse events, were noted during the course of treatment. DISCUSSION: Octreotide is considered the antidote for sulfonylurea-induced hypoglycemia. It may be especially useful in patients with congestive heart failure who may not tolerate intravenous infusions of dextrose. The package insert cautions of the occurrence of cardiac adverse effects such as bradycardia, heart block, and worsening heart failure. Patients with heart failure may theoretically be at a higher risk of these adverse effects due to the concurrent use of atrioventricular blocking agents. However, a review of current literature reveals that the adverse effect profile depends on the route, dose, and formulation of the octreotide used along with the clinical indication. These adverse effects may not be clinically significant with the doses used for treatment of sulfonylurea-induced hypoglycemia and the benefits of the drug may outweigh the risks. CONCLUSIONS: In these cases, octreotide was safely and effectively used in the treatment of sulfonylurea-induced hypoglycemia in patients with congestive heart failure by adhering to dosing guidelines and close monitoring.

Accidental Overdose of Tiotropium in a Patient with Atrial Fibrillation (February)

OBJECTIVE: To report a case of refractory tachycardia after an excessive dose of inhaled tiotropium. CASE SUMMARY: A 74-year-old male with atrial fibrillation was admitted for increased heart rate and shortness of breath. The patient's heart rate was initially stabilized between 80 and 90 beats/min with metoprolol succinate 50 mg daily. During hospitalization, he accidentally received 5 capsules of tiotropium 18 µg inhaled as a single dose (total 90 µg) and, approximately 15 minutes later, his heart rate increased from 80 to 160 beats/min. Over 5 days of hospitalization, the patient's tachycardia was difficult to control and he required multiple atrioventricular (AV) nodal blocking agents (physostigmine, metoprolol tartrate, diltiazem) for effective stabilization prior to discharge. On outpatient follow-up 11 days after the ingestion the patient's heart rate was in the 40s and the AV nodal blocking agents were proportionately decreased. DISCUSSION: Tiotropium is a long-acting anticholinergic medication used to treat chronic obstructive pulmonary disease. Little has been reported as to the potential systemic toxicities of tiotropium. Tachycardia is listed as a potential adverse effect, but based on a MEDLINE search (1966-July 2009) using tiotropium, tachycardia, and overdose as search terms, there have been no case reports published. Renal impairment may increase plasma concentrations of tiotropium; our patient's creatinine clearance was estimated to be below 50 mL/min. According to the Naranjo probability scale, our patient's development of tachycardia was probably associated with tiotropium inhalation. CONCLUSIONS: Tiotropium can be temporally implicated in a rapid heart rate following excessive ingestion. Health care professionals should be aware of tachycardic effects of tiotropium, particularly in patients with underlying structural heart disease, atrial fibrillation, and renal impairment.

Update on Pressure Ulcer Management and Deep Tissue Injury (February)

OBJECTIVE: To review recent literature regarding therapeutic management of pressure ulcers and to discuss the potential implications of the newly recognized entity, deep tissue injury (DTI). DATA SOURCES: A MEDLINE search was conducted of pressure ulcer therapy published between January 2001 and October 2009. Key search terms included pressure ulcers, deep tissue injury, nutrition, antibiotics, and therapy. STUDY SELECTION AND DATA EXTRACTION: Comparative clinical trials involving pharmacologic agents in the treatment of pressure ulcers and DTI were evaluated. Included trials were those with defined interventions and outcome parameters for wound healing. DATA SYNTHESIS: Pressure ulcers remain an important issue in the care of elderly and immobilized patients. DTI has been recently added by the National Pressure Ulcer Advisory Panel as a separate category in the staging of pressure ulcers. There is currently a lack of consensus on how to identify and treat DTI, but preventive measures typically employed in the management of all pressure ulcers have been recommended. Recent studies on topical phenytoin, silver preparations, and growth factors report benefit in the management of pressure ulcers. However, studies evaluating these treatment approaches often lack the sample size necessary to adequately support recommendations. CONCLUSIONS: Determining the extent of tissue damage in DTI is currently not possible. Therefore, management recommendations focus on limiting extension of the ulcer stage through preventive strategies. Routine use of topical phenytoin, silver preparations, or growth factors in therapy of pressure ulcers cannot be recommended until more data from rigorously designed studies are available.

Certolizumab Pegol: A TNF-{alpha} Antagonist for the Treatment of Moderate-to-Severe Crohn's Disease (February) (CE)

OBJECTIVE: To review certolizumab pegol for the treatment of moderate-to-severe Crohn's disease (CD). DATA SOURCES: Clinical studies were identified through MEDLINE (1966-October 1, 2009), bibliographies of articles, International Pharmaceutical Abstracts, clinicaltrials.gov, fda.gov, and New Drug Approval documents (www.accessdata. fda.gov). Search terms were CDP 870, certolizumab pegol, Cimzia, Crohn's disease, and inflammatory bowel disease. STUDY SELECTION AND DATA EXTRACTION: Human studies describing pharmacology, pharmacokinetics, efficacy, and safety of certolizumab pegol were identified. Phase 2 and Phase 3 randomized controlled trials and observational studies were reviewed, with emphasis given to Phase 2 and Phase 3 trials. DATA SYNTHESIS: Certolizumab pegol is a tumor necrosis factor-alfa (TNF-) antagonist, approved for the treatment of moderate-to-severe CD that is failing conventional therapy. It is an antigen-binding fragment (Fab') portion of an immunoglobulin G antibody attached to a polyethylene glycol moiety. In 2 Phase 3 randomized, placebo-controlled trials, certolizumab pegol was effective in inducing clinical response compared with placebo. Common adverse effects during clinical trials were upper respiratory tract infection, urinary tract infection, and arthralgia. Serious infection occurred in 3% of patients. The 4 published controlled trials for the use of certolizumab pegol in the treatment of CD share similar limitations with other studies of TNF- antagonists including high placebo response, natural course of disease fluctuation, and the use of Crohn's Disease Activity Index to assess outcomes. However, certolizumab pegol is an effective agent for adults with moderate-to-severe CD with less than optimal response to conventional therapy. Long-term efficacy and safety data are unavailable. Certolizumab pegol and adalimumab, unlike infliximab, can be self-administered. CONCLUSIONS: With similarity in cost and the lack of head-to-head comparisons, patient and physician preference may determine choice of TNF- antagonist.

Lofexidine, an {alpha}2-Receptor Agonist for Opioid Detoxification (February) (CE)

OBJECTIVE: To review the pharmacology, toxicology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines for lofexidine, an 2- agonist, for opioid detoxification. DATA SOURCES: Primary literature was identified through a MEDLINE search (1950-September 2009), EMBASE (1988-July 2009), International Pharmaceutical Abstracts (1970-September 2009), and the Cochrane Library (1996- September 2009) using the key words lofexidine and opioid withdrawal. Abstracts were included in the absence of published results of studies. STUDY SELECTION AND DATA EXTRACTION: Studies published in English-language literature reporting on animal and human pharmacology, toxicology, and pharmacokinetics were included in addition to clinical trials using lofexidine for opioid detoxification in comparison to placebo or active controls. DATA SYNTHESIS: Lofexidine is an 2-agonist structurally related to clonidine. It is not an effective antihypertensive agent; however, it decreases the sympathetic outflow responsible for many opioid withdrawal symptoms. Nine clinical studies were reviewed representing 354 patients receiving lofexidine including a recent Phase 3 clinical trial. Eight studies involved comparisons of lofexidine to an opioid receptor agonist or clonidine for opioid detoxification. In these trials, lofexidine dosing was titrated to a maximum of 1.6-3.2 mg/day in divided doses for a total of 5-18 days. The data suggest that lofexidine has positive efficacy in reducing opioid withdrawal symptoms and is at least as effective as the opioid receptor agonists utilized for detoxification. Not all withdrawal symptoms are alleviated by 2-agonists, with many patients complaining of insomnia and aching. The most common adverse event with lofexidine in the Phase 3 trial was insomnia. Hypotension was also reported; however, the studies comparing clonidine with lofexidine suggest decreased incidence and severity of adverse events with lofexidine. CONCLUSIONS: Lofexidine appears to be a promising agent for opioid detoxification. If approved, it would be the first nonopioid agent approved for this indication. Further large-scale controlled studies are needed to identify the safest, most effective dosage regimen required to achieve opioid detoxification.

Raltegravir-Based HAART Regimen in a Patient with Large B-Cell Lymphoma (February)

OBJECTIVE: To describe the antiretroviral management of a patient diagnosed simultaneously with HIV/AIDS and diffuse large B-cell lymphoma, focusing on the drug-drug interactions between highly active antiretroviral therapy (HAART) and concomitant cancer chemotherapy. CASE SUMMARY: A 55-year-old white man was recently diagnosed with HIV/AIDS and presented 1 month later with complaints of nausea, vomiting, abdominal pain, double vision, right eye discomfort/swelling, and a 3.6-kg weight loss. An excisional biopsy of a right inguinal lymph node confirmed a new diagnosis of diffuse large B-cell lymphoma. HAART and a chemotherapeutic regimen, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with intrathecal methotrexate, was to be initiated. As the potential for multiple drug-drug interactions existed, raltegravir, abacavir, and lamivudine were chosen for the initial HAART regimen. The patient achieved and maintained an undetectable viral load throughout 6 CHOP cycles. DISCUSSION: HAART improves the chemotherapeutic response in patients with HIV and lymphoma. Multiple drug-drug interactions are possible in patients who are to receive CHOP and HAART. Cyclophosphamide and vincristine are metabolized via the CYP3A4 isoenzyme. Protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors both inhibit and induce CYP3A4, with the potential for altered chemotherapeutic and cytotoxic effects. When PIs are combined with CHOP, mortality is reduced, but increased adverse effects are demonstrated. Raltegravir, an integrase inhibitor, is eliminated via glucuronidation and results in minimal drug-drug interactions. Raltegravir improves virologic and immunologic responses in HAART-naïve patients and thus would be a suitable alternative for preventing chemotherapeutic-HAART interactions. CONCLUSIONS: There is limited information published regarding the potential for interactions between HAART and cancer chemotherapy. While further research is necessary, it is important for clinicians to consider the potential for drug-drug interactions when designing a HAART regimen concurrently with chemotherapy.

Safety Considerations and Potential Interactions of Vitamins: Should Vitamins Be Considered Drugs? (February)

OBJECTIVE: To examine adverse effects, adverse events, and potential interactions of vitamins in light of their current prevalence of use, and to discuss whether vitamins should be considered over-the-counter drugs or natural health products/dietary supplements. DATA SOURCES: We performed a MEDLINE/PubMed search, explored 4 online databases (Medline Plus, Drug Digest, Natural Medicine Comprehensive Database, and the database of the University of Maryland), and examined reference lists of included studies published from 1966 through October 2009. STUDY SELECTION AND DATA EXTRACTION: The studies were reviewed, with an emphasis on randomized controlled clinical trials. We included articles with the most clinically important information with regard to adverse events and interactions. DATA SYNTHESIS: Vitamins are used by over one third of the North American population. Vitamins have documented adverse effects and toxicities, and most have documented interactions with drugs. While some vitamins (biotin, pantothenic acid, riboflavin, thiamine, vitamin B12, vitamin K) have minor and reversible adverse effects, others, such as fat-soluble vitamins (A, E, D), can cause serious adverse events. Two water-soluble vitamins, folic acid and niacin, can also have significant toxicities and adverse events. CONCLUSIONS: Our recommendation is that vitamins A, E, D, folic acid, and niacin should be categorized as over-the-counter medications. Labeling of vitamins, especially those intended for children and other vulnerable groups, should include information on possible toxicities, dosing, recommended upper intake limits, and concurrent use with other products. Vitamin A should be excluded from multivitamin supplements and food fortificants.

In This Issue

In This Issue Clinical Pharmacology & Therapeutics 87, 1 (January 2010). doi:10.1038/clpt.2009.256

Drug Transporters: Recent Advances and Therapeutic Applications

Drug Transporters: Recent Advances and Therapeutic Applications Clinical Pharmacology & Therapeutics 87, 3 (January 2010). doi:10.1038/clpt.2009.239 Authors: R M Franke & A Sparreboom

Highlights

Highlights Clinical Pharmacology & Therapeutics 87, 8 (January 2010). doi:10.1038/clpt.2009.257 Author:

ASCPT News

ASCPT News Clinical Pharmacology & Therapeutics 87, 10 (January 2010). doi:10.1038/clpt.2009.238

Transporters in Drug-Refractory Epilepsy: Clinical Significance

Transporters in Drug-Refractory Epilepsy: Clinical Significance Clinical Pharmacology & Therapeutics 87, 13 (January 2010). doi:10.1038/clpt.2009.225 Authors: N Marchi, J Gonzalez-Martinez, M-T Nguyen, T Granata & D Janigro

ABC Transporters in Drug-Refractory Epilepsy: Limited Clinical Significance of Pharmacogenetics?

ABC Transporters in Drug-Refractory Epilepsy: Limited Clinical Significance of Pharmacogenetics? Clinical Pharmacology & Therapeutics 87, 15 (January 2010). doi:10.1038/clpt.2009.237 Author: I Cascorbi

A Piece in the Puzzle of Personalized Medicine

A Piece in the Puzzle of Personalized Medicine Clinical Pharmacology & Therapeutics 87, 19 (January 2010). doi:10.1038/clpt.2009.219 Authors: H K Kroemer, H E Meyer & zu Schwabedissen

Biomarker Qualification via Public–Private Partnerships

Biomarker Qualification via Public–Private Partnerships Clinical Pharmacology & Therapeutics 87, 21 (January 2010). doi:10.1038/clpt.2009.193 Authors: S L Eck & S M Paul

Quantification of T-Cell Proliferation for Individualizing Immunosuppressive Therapy for Transplantation Patients

Quantification of T-Cell Proliferation for Individualizing Immunosuppressive Therapy for Transplantation Patients Clinical Pharmacology & Therapeutics 87, 23 (January 2010). doi:10.1038/clpt.2009.171 Author: H Ohdan

Expediting Patients’ Access to Medicines by Improving the Predictability of Drug Development and the Regulatory Approval Process

Expediting Patients’ Access to Medicines by Improving the Predictability of Drug Development and the Regulatory Approval Process Clinical Pharmacology & Therapeutics 87, 27 (January 2010). doi:10.1038/clpt.2009.179 Authors: L Liberti, A Breckenridge, H G Eichler, R Peterson, N McAuslane & S Walker

The International Transporter Consortium: A Collaborative Group of Scientists From Academia, Industry, and the FDA

The International Transporter Consortium: A Collaborative Group of Scientists From Academia, Industry, and the FDA Clinical Pharmacology & Therapeutics 87, 32 (January 2010). doi:10.1038/clpt.2009.236 Authors: S-M Huang, L Zhang & K M Giacomini

Rupatadine and Heart Rhythm Disturbances

Rupatadine and Heart Rhythm Disturbances Clinical Pharmacology & Therapeutics 87, 37 (January 2010). doi:10.1038/clpt.2009.118 Authors: R Fité & J Borja

Response to “Rupatadine and Heart Rhythm Disturbances”

Response to “Rupatadine and Heart Rhythm Disturbances” Clinical Pharmacology & Therapeutics 87, 37 (January 2010). doi:10.1038/clpt.2009.157 Authors: A Carvajal, D Macías, I Salado, M Sáinz, S Ortega, C Campo, J García del Pozo, L H Martín Arias, A Velasco, S Gonçalves, R Pombal & R Carmona

Drug Uptake Systems in Liver and Kidney: A Historic Perspective

Drug Uptake Systems in Liver and Kidney: A Historic Perspective Clinical Pharmacology & Therapeutics 87, 39 (January 2010). doi:10.1038/clpt.2009.235 Author: B Hagenbuch

Comparison of Critical Drug–Drug Interaction Listings: The Department of Veterans Affairs Medical System and Standard Reference Compendia

Comparison of Critical Drug–Drug Interaction Listings: The Department of Veterans Affairs Medical System and Standard Reference Compendia Clinical Pharmacology & Therapeutics 87, 48 (January 2010). doi:10.1038/clpt.2009.198 Authors: E L Olvey, S Clauschee & D C Malone

Loss-of-Function CYP2C9 Variants Improve Therapeutic Response to Sulfonylureas in Type 2 Diabetes: A Go-DARTS Study

Loss-of-Function CYP2C9 Variants Improve Therapeutic Response to Sulfonylureas in Type 2 Diabetes: A Go-DARTS Study Clinical Pharmacology & Therapeutics 87, 52 (January 2010). doi:10.1038/clpt.2009.176 Authors: K Zhou, L Donnelly, L Burch, R Tavendale, A S F Doney, G Leese, A T Hattersley, M I McCarthy, A D Morris, C C Lang, C N A Palmer & E R Pearson

Genetic Factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) Are Predictor Variables for Warfarin Response in Very Elderly, Frail Inpatients

Genetic Factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) Are Predictor Variables for Warfarin Response in Very Elderly, Frail Inpatients Clinical Pharmacology & Therapeutics 87, 57 (January 2010). doi:10.1038/clpt.2009.178 Authors: E Pautas, C Moreau, I Gouin-Thibault, J-L Golmard, I Mahé, C Legendre, E Taillandier-Hériche, B Durand-Gasselin, A-M Houllier, P Verrier, P Beaune, M-A Loriot & V Siguret

UDP-Glucuronosyltransferase (UGT) Polymorphisms Affect Atorvastatin Lactonization In Vitro and In Vivo

UDP-Glucuronosyltransferase (UGT) Polymorphisms Affect Atorvastatin Lactonization In Vitro and In Vivo Clinical Pharmacology & Therapeutics 87, 65 (January 2010). doi:10.1038/clpt.2009.181 Authors: S Riedmaier, K Klein, U Hofmann, J E Keskitalo, P J Neuvonen, M Schwab, M Niemi & U M Zanger

A Pharmacovigilance Program From Laboratory Signals for the Detection and Reporting of Serious Adverse Drug Reactions in Hospitalized Patients

A Pharmacovigilance Program From Laboratory Signals for the Detection and Reporting of Serious Adverse Drug Reactions in Hospitalized Patients Clinical Pharmacology & Therapeutics 87, 74 (January 2010). doi:10.1038/clpt.2009.185 Authors: E Ramirez, A J Carcas, A M Borobia, S H Lei, E Piñana, S Fudio & J Frias

Ocular Hemodynamic Effects of Nitrovasodilators in Healthy Subjects

Ocular Hemodynamic Effects of Nitrovasodilators in Healthy Subjects Clinical Pharmacology & Therapeutics 87, 87 (January 2010). doi:10.1038/clpt.2009.186 Authors: D Schmidl, E Polska, B Kiss, S Sacu, G Garhofer & L Schmetterer

Safety and Pharmacokinetics of Repeat-Dose Micafungin in Young Infants

Safety and Pharmacokinetics of Repeat-Dose Micafungin in Young Infants Clinical Pharmacology & Therapeutics 87, 93 (January 2010). doi:10.1038/clpt.2009.200 Authors: D K Benjamin, P B Smith, A Arrieta, L Castro, P J Sánchez, D Kaufman, L J Arnold, L L Kovanda, T Sawamoto, D N Buell, W W Hope & T J Walsh

The Role of Organic Anion–Transporting Polypeptides and Their Common Genetic Variants in Mycophenolic Acid Pharmacokinetics

The Role of Organic Anion–Transporting Polypeptides and Their Common Genetic Variants in Mycophenolic Acid Pharmacokinetics Clinical Pharmacology & Therapeutics 87, 100 (January 2010). doi:10.1038/clpt.2009.205 Authors: N Picard, S W Yee, J-B Woillard, Y Lebranchu, Y Le Meur, K M Giacomini & P Marquet

The Pharmacogenomics of Membrane Transporters Project: Research at the Interface of Genomics and Transporter Pharmacology

The Pharmacogenomics of Membrane Transporters Project: Research at the Interface of Genomics and Transporter Pharmacology Clinical Pharmacology & Therapeutics 87, 109 (January 2010). doi:10.1038/clpt.2009.226 Authors: D L Kroetz, S W Yee & K M Giacomini

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