Pharmacology RSS : Gourt

Stimulus Grant To Help MSU Team Improve Drug Development From Plants

Scientists at Michigan State University are receiving nearly $3 million from the National Institutes of Health to uncover how several popular plants make medicinal compounds.

Novexel Starts Phase II Clinical Trial With NXL103 In Adults With Acute Bacterial Skin And Skin Structure Infections (ABSSSI)

Novexel, a speciality pharmaceutical company focused on the discovery and development of novel antibiotics designed to overcome the significant global problem of microbial resistance, announces that its most advanced oral antibacterial NXL103 (flopristin/linopristin), has started a Phase II clinical trial in adults with acute bacterial skin and skin structure infections (ABSSSI).

Oncolytics Biotech(R) Inc. Collaborators Present Positive Phase II Sarcoma Trial Results At CTOS Annual Meeting

Oncolytics Biotech Inc. (TSX:ONC, NASDAQ:ONCY) ("Oncolytics" or the "Company") announced updated results from a Phase II study of intravenous REOLYSIN(R) in patients with sarcomas metastatic to the lung in a poster presentation at the 15th Annual Connective Tissue Oncology Society Meeting held in Miami Beach, Florida, from November 5th to 7th.

DNA Molecules In Moss Open Door To New Biotechnology

Plasmids, which are DNA molecules capable of independent replication in cells, have played an important role in gene technology. Researchers from Uppsala University in Sweden have now demonstrated that plasmid-based methods, which had been limited to single-cell organisms such as bacteria and yeasts, can be extended to mosses, opening the door to applications of a number of powerful techniques in plant research.

Novartis Receives Regulatory Approval In Germany For Celtura®, A Cell Culture-based Influenza A(H1N1) Pandemic Vaccine

Novartis announced that it received approval from the German regulatory authorities for its adjuvanted cell culture-based Influenza A(H1N1) 2009 monovalent vaccine, Celtura®. Novartis continues to pursue registration in other major countries, including Japan and Switzerland.

Lundbeck Starts Clinical Phase IIa With Lu AA24493 (cEPO) In Friedreich's Ataxia In A Study Also Assessing Efficacy Via Biomarkers

H. Lundbeck A/S strengthens its pipeline of pharmaceuticals in clinical development by initiating phase IIa clinical studies with the innovative project Lu AA24493 in order to evaluate safety and tolerability and to explore theoretical efficacy parameters of the drug in humans. Lundbeck expects to enrol 35-40 people suffering from Friedreich's ataxia in this study.

Ag Biotech Industry Stands Behind IRM Program

The agricultural biotechnology industry maintains that the Insect Resistance Management (IRM) Plan has been one of the most successful industry stewardship programs implemented since pest-tolerant biotech crops were introduced more than a decade ago. A report released today by the Center for Science in the Public Interest (CSPI) alleges that farmer compliance with the insect-resistance management requirement has declined somewhat in recent years.

DOJ Investigates Alleged Fraud By Drugmakers; Sanctions On WellCare Lifted

News outlets focus on alleged fraud in the drug and insurance industries. "A $112 million settlement involving alleged drug kickbacks that the Justice Dept. announced with the nation's largest nursing home pharmacy and a generic drug manufacturer on Nov. 3 is part of a wide-ranging investigation of suspected Medicaid fraud by the pharmaceutical industry,"

Wall Street Journal Examines Big Pharma's 'Growing Interest' In Emerging-Market Vaccine Development, Production

The Wall Street Journal examines "big pharma's growing interest in a corner of healthcare - emerging-market inoculations," in light of a recent move by Novartis to purchase an 85 percent stake in the Chinese vaccine maker Zhejiang Tianyuan Bio-Pharmaceutical Co.

Helix BioPharma Corp. Completes Enrollment In Its Phase II Trial Of Topical Interferon Alpha-2b In Patients With Ano-Genital Warts

Helix BioPharma Corp. (TSX, FSE: "HBP" / OTCQX: HXBPF) announced that its Phase II trial of Topical Interferon Alpha-2b for the treatment of ano-genital warts (AGW) has completed patient enrollment, with the required 120th patient randomized to enter the trial. The double-blind and placebo-controlled Phase II trial is underway at multiple centers in Germany and Sweden.

Pivotal Data Published In The Journal Cancer Demonstrate That TREANDA Induced Durable Responses In Relapsed Indolent Non-Hodgkin's Lymphoma

Cephalon, Inc. (Nasdaq: CEPH) announced the journal Cancer has published a pivotal study demonstrating that TREANDA® (bendamustine HCl) for Injection induced durable responses in patients with indolent B-cell non-Hodgkin's lymphoma (NHL) whose disease had progressed during or within six months of treatment with rituximab.

Amgen Announces Overall Survival Results For Vectibix(R) In First-Line Metastatic Colorectal Cancer

Amgen (Nasdaq: AMGN) announced that the Phase 3 PRIME "203" trial evaluating Vectibix® (panitumumab) administered in combination with FOLFOX (an oxaliplatin-based chemotherapy) as a first-line treatment of metastatic colorectal cancer (mCRC) failed to meet a secondary endpoint of overall survival.

Sunesis' Voreloxin Receives FDA Orphan Drug Designation For Acute Myeloid Leukemia

Sunesis Pharmaceuticals, Inc. (Nasdaq: SNSS) announced that the U.S. Food and Drug Administration has granted voreloxin orphan drug designation for the treatment of acute myeloid leukemia (AML).

Man Sentenced For Sale And Supply Of Controlled And Counterfeit Drugs

A 41-year-old man, Mr Harish Gami, received an eight month prison sentence suspended for two years at Aylesbury Crown Court today for the illicit sale and supply of controlled drugs as well as counterfeit and unlicensed medicines. The Medicines and Healthcare products Regulatory Agency (MHRA) discovered more than 86,000 Valium tablets and a further 11,500 medicinal products in an undercover investigation into Gami's illegal online dealing.

The Creation Of A New Niche Specialty Pharmaceutical Company Focused On Rare Diseases - With Strong Cash Flow Generation And Growth Potential

Biovitrum and Swedish Orphan will be combined forming Swedish Orphan Biovitrum with pro forma revenues 2009 of approximately SEK 2 billion and an EBITDA margin of 15 percent. Biovitrum will pay an upfront consideration of SEK 3.5 billion (on a cash and debt free basis), to be financed by a fully guaranteed rights issue, an issue in kind and bank financing. The Transaction will be instantly accretive to earnings per share for Biovitrum's shareholders. Shared mission.

Conflicts Of Interest Examined Between Doctors And Medical Industry, AARP And Reform

Health care reform bills include provisions to examine the financial relationships between doctors and the medical industry while some are questioning the AARP's role in reform.

ViraCor-IBT Laboratories To Present At The American College Of Allergy, Asthma And Immunology's Annual Meeting

Scientists from ViraCor-IBT Laboratories have been selected to provide four oral presentations and one poster presentation at this year's American College of Allergy, Asthma and Immunology's Annual Scientific Meeting in Miami, Florida. Michelle Altrich, PhD, HCLD (ABB), and Michael Ling, PhD, will present data on a wide range of topics including Filaggrin, Pneumococcal Antibody Avidity, Chronic Urticaria, Drug Hypersensitivity Reactions and T-Cell Excision Circles.

FDA Unveils Safe Use Initiative That Targets Preventable Harm From Medication Use

The U.S. Food and Drug Administration announced the Safe Use Initiative, a program aimed at reducing the likelihood of preventable harm from medication use. "Too many people suffer unnecessary injuries from avoidable medication misuse, errors and other problems. The FDA is launching the Safe Use Initiative to develop targeted solutions for reducing these injuries," said FDA Commissioner Margaret A. Hamburg, M.D.

Drug Company-sponsored Events For Health Professionals Fail To Disclose Financial Ties

Australian reporting standards for disclosing the ties between pharmaceutical companies and health professionals are not comprehensive enough, according to an analysis in this weeks PLoS Medicine.

FDA Awards Absorption Systems Phase II SBIR Grant For CellPort Technologies™

Absorption Systems LP announced that it has been awarded a Phase II Small Business Innovation Research (SBIR) grant from the U.S. Food and Drug Administration (FDA) to continue development of the company's CellPort Technologies™ testing platform. This unique assay platform enables more specific prediction of potential drug-drug interactions mediated by human drug transport proteins.

GlaxoSmithKline, Pfizer Formally Launch Company To Develop New HIV Treatments

Pharmaceutical companies GlaxoSmithKline (GSK) and Pfizer on Tuesday formally launched ViiV Healthcare, a company focused on the development of new HIV treatments, Dow Jones Newswires/SmartMoney.com reports (11/3).

Study Points To New Uses, Unexpected Side Effects Of Already-existing Drugs

Scientists at the University of North Carolina at Chapel Hill School of Medicine and the University of California, San Francisco have developed and experimentally tested a technique to predict new target diseases for existing drugs. The researchers developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring binding partners -- known as ligands -- of disease targets within the cell.

Aerovance Completes Patient Enrollment In Phase 2b Clinical Trial Of Aerovant(TM) For Treatment Of Uncontrolled Asthma

Aerovance Inc. announced it has completed patient enrollment in a Phase 2b clinical trial of the inhaled dry powder formulation of Aerovant for the treatment of uncontrolled asthma. Top-line results are expected by the second quarter of 2010. Named AeroTrial(TM), the study enrolled approximately 540 patients at 75 sites in the United States and Europe.

Experts Propose 'Global Health Accellerator' To Help New Drugs, Diagnostics, Vaccines Reach Distant Markets

Research firms in developing countries have a medicine cabinet full of affordable and innovative drugs, diagnostics and vaccines on shelves or in development to address "neglected tropical diseases" but need help to get such products to more potential users.

MEPs And Industry Debate Shared Commitment To Deliver 21st Century Healthcare Systems In Times Of Crisis

European policymakers and the pharmaceutical industry need to work collaboratively to ensure the current financial crisis does not stand in the way of delivering healthcare systems fit for the 21st century. Representatives of EFPIA, the voice of the research-based pharmaceutical industry in Europe, and MEPs involved in healthcare issues discussed a common agenda to shape the future of healthcare in Europe.

Multidrug-Resistant Enterococcus faecium Endocarditis Treated with Combination Tigecycline and High-Dose Daptomycin (December)

OBJECTIVE: To report a case of multidrug-resistant Enterococcus faecium requiring combination antibacterial therapy. CASE SUMMARY: A 39-year-old female presented with chest pain and a history of endocarditis 3 years prior to admission. Blood cultures were positive for E. faecium. She was treated initially with daptomycin 6 mg/kg daily, which was later increased to 8 mg/kg daily despite poor gentamicin clearance. A variety of antibiotics were used in combination with daptomycin, but the patient remained febrile, with positive blood cultures revealing vancomycin minimum inhibitory concentration (MIC) greater than 256 µg/mL and daptomycin MIC 3 µg/mL (and later, 4 µg/mL). Following the addition of tigecycline, the patient experienced rapid clinical and microbiologic improvement, and blood cultures remained negative 9 weeks after discharge. DISCUSSION: Limited clinical data support the use of daptomycin for the treatment of E. faecium endocarditis, and information regarding the effects of escalating doses and combination therapy is scant. After failing multiple combination regimens, this patient responded to a combination of tigecycline and daptomycin. Daptomycin 8 mg/kg daily did not result in creatine kinase elevation in the face of evidence of possible renal dysfunction. CONCLUSIONS: Increasing doses of daptomycin may enhance efficacy without compromising safety, even in patients with some renal dysfunction. The combination of daptomycin and tigecycline may be useful for the treatment of multi-drug- resistant E. faecium.

Prevalence and Risk Factors for Acute Kidney Injury Associated with Parenteral Polymyxin B Use(December)

BACKGROUND: The main adverse effect of polymyxin B is nephrotoxicity. There are few data on polymyxin-associated renal injury. OBJECTIVE: To assess the prevalence of and risk factors for acute kidney injury (AKI) in patients treated with polymyxin B. METHODS: The studied population included 114 patients who received at least 3 consecutive days of intravenous polymyxin B and had baseline serum creatinine (SCr) and at least one further SCr measurement during treatment. AKI was defined as an SCr increase to 1.8 mg/dL or greater in patients with baseline SCr less than 1.5 mg/dL, or an increase greater than or equal to 50% in baseline SCr when it was already greater than or equal to 1.5 mg/dL, or need for dialysis. RESULTS: AKI developed in 22% of the patients. They were older, had a higher baseline SCr, had a higher frequency of baseline SCr greater than or equal to 1.5 mg/dL, used other nephrotoxic drugs and furosemide more often, and required vasoactive drugs and mechanical ventilation more frequently. Progression to renal failure was significantly more probable when the bacteria were isolated in the abdomen, catheter, or blood. AKI patients had a higher mortality rate (92% vs 53%; p < 0.001). Logistic regression identified abnormal baseline SCr (odds ratio [OR] 3.51); need for vasoactive drugs (OR 3.03); and abdomen, blood, or catheter as the infection site (OR 3.82) as independent risk factors for AKI. CONCLUSIONS: Patients who developed AKI had a strikingly elevated mortality rate. Polymyxin B should be used with extreme caution in patients who have an abnormal baseline SCr; use vasoactive drugs; or have abdomen, blood, or catheter as the infection site.

Sorafenib-Induced Hepatic Encephalopathy (December)

Successful Use of Topical Voriconazole 1% Alone as First-Line Antifungal Therapy Against Candida albicans Keratitis (December)

OBJECTIVE: To report the successful use of topical voriconazole 1% given alone as primary therapy against a case of Candida albicans keratitis. CASE SUMMARY: A 48-year-old previously well man presented to the emergency department with pain and foreign body sensation in the left eye following exposure to dust while driving a forklift. He wore weekly disposable soft contact lenses. Anterior stromal scar and dense infiltrate were detected in the left eye. The anterior chamber remained deep, with flare and copious white cells. Intraocular pressure was 12 mm Hg and visual acuity was 20/200. The epithelial defect persisted, with progressive thinning despite topical fluorometholone and ofloxacin 0.3% therapy for 2 days. Microbiology testing revealed C. albicans as the affecting pathogen. Hourly administration of voriconazole 1% eye drops was initiated as antifungal therapy. The corneal infiltrate began to resolve and the epithelial defect decreased in size within 2 days. Visual acuity improved to 20/120. After 4 days of voriconazole use, the epithelial defect was completely healed and visual acuity was 20/30 in the affected eye. No fungi were isolated from a second eye scrape. DISCUSSION: Topical voriconazole as salvage monotherapy to manage fungal keratitis has been previously reported. It can be argued, however, that the primary therapy has facilitated the positive response to subsequent topical voriconazole. To date, there has been no solid evidence to suggest that topical voriconazole is effective when used as primary therapy. The current report provides evidence of topical voriconazole demonstrating clinical success when used as first-line therapy to treat C. albicans keratitis. The use of topical voriconazole can reduce the costs, toxicity, and drug interactions associated with common antifungal therapies. CONCLUSIONS: Topical voriconazole 1% eye drops administered alone demonstrated success as first-line therapy against the most common fungal keratitis, C. albicans keratitis.

In This Issue

In This Issue Clinical Pharmacology & Therapeutics 86, 451 (November 2009). doi:10.1038/clpt.2009.202

Nephropharmacology: Drugs and the Kidney

Nephropharmacology: Drugs and the Kidney Clinical Pharmacology & Therapeutics 86, 453 (November 2009). doi:10.1038/clpt.2009.191 Authors: A J Atkinson & S-M Huang

Highlights

Highlights Clinical Pharmacology & Therapeutics 86, 458 (November 2009). doi:10.1038/clpt.2009.203 Author:

ASCPT News

ASCPT News Clinical Pharmacology & Therapeutics 86, 460 (November 2009). doi:10.1038/clpt.2009.196

Clinical Physiology and Pharmacology: The Essentials

Clinical Physiology and Pharmacology: The Essentials Clinical Pharmacology & Therapeutics 86, 462 (November 2009). doi:10.1038/clpt.2009.189 Author: M J Avram

Use of the MDRD Study Equation to Estimate Kidney Function for Drug Dosing

Use of the MDRD Study Equation to Estimate Kidney Function for Drug Dosing Clinical Pharmacology & Therapeutics 86, 465 (November 2009). doi:10.1038/clpt.2009.124 Authors: L A Stevens & A S Levey

Continuing the Use of the Cockcroft–Gault Equation for Drug Dosing in Patients With Impaired Renal Function

Continuing the Use of the Cockcroft–Gault Equation for Drug Dosing in Patients With Impaired Renal Function Clinical Pharmacology & Therapeutics 86, 468 (November 2009). doi:10.1038/clpt.2009.187 Authors: W J Spruill, W E Wade & H H Cobb

How a US Regulator Can Encourage New Science

How a US Regulator Can Encourage New Science Clinical Pharmacology & Therapeutics 86, 471 (November 2009). doi:10.1038/clpt.2009.188 Author: D C Throckmorton

How Will GINA Influence Participation in Pharmacogenomics Research and Clinical Testing?

How Will GINA Influence Participation in Pharmacogenomics Research and Clinical Testing? Clinical Pharmacology & Therapeutics 86, 472 (November 2009). doi:10.1038/clpt.2009.146 Authors: L G Dressler & S F Terry

When to Conduct a Renal Impairment Study During Drug Development: US Food and Drug Administration Perspective

When to Conduct a Renal Impairment Study During Drug Development: US Food and Drug Administration Perspective Clinical Pharmacology & Therapeutics 86, 475 (November 2009). doi:10.1038/clpt.2009.190 Authors: S-M Huang, R Temple, S Xiao, L Zhang & L J Lesko

Challenges in Developing Evidence-Based Drug Dosing Guidelines for Adults and Children Receiving Renal Replacement Therapy

Challenges in Developing Evidence-Based Drug Dosing Guidelines for Adults and Children Receiving Renal Replacement Therapy Clinical Pharmacology & Therapeutics 86, 479 (November 2009). doi:10.1038/clpt.2009.150 Authors: B A Mueller & W E Smoyer

Drug Dosing in Patients With Impaired Renal Function

Drug Dosing in Patients With Impaired Renal Function Clinical Pharmacology & Therapeutics 86, 483 (November 2009). doi:10.1038/clpt.2009.135 Author: D C Brater

Novel Biomarkers of Acute Kidney Toxicity

Novel Biomarkers of Acute Kidney Toxicity Clinical Pharmacology & Therapeutics 86, 490 (November 2009). doi:10.1038/clpt.2009.149 Authors: F M Goodsaid, M Blank, F Dieterle, P Harlow, E Hausner, F Sistare, A Thompson & J Vonderscher

Population Analyses of Atorvastatin Clearance in Patients Living in the Community and in Nursing Homes

Population Analyses of Atorvastatin Clearance in Patients Living in the Community and in Nursing Homes Clinical Pharmacology & Therapeutics 86, 497 (November 2009). doi:10.1038/clpt.2009.100 Authors: J B Schwartz & D Verotta

Comparison of Manual and Automated Measurements of the QT Interval in Healthy Volunteers: An Analysis of Five Thorough QT Studies

Comparison of Manual and Automated Measurements of the QT Interval in Healthy Volunteers: An Analysis of Five Thorough QT Studies Clinical Pharmacology & Therapeutics 86, 503 (November 2009). doi:10.1038/clpt.2009.34 Authors: C Fosser, G Duczynski, M Agin, P Wicker & B Darpo

Systematic Evaluation of Drug–Disease Relationships to Identify Leads for Novel Drug Uses

Systematic Evaluation of Drug–Disease Relationships to Identify Leads for Novel Drug Uses Clinical Pharmacology & Therapeutics 86, 507 (November 2009). doi:10.1038/clpt.2009.103 Authors: A P Chiang & A J Butte

Association of CYP2B6, CYP3A5, and CYP2C19 Genetic Polymorphisms With Sibutramine Pharmacokinetics in Healthy Korean Subjects

Association of CYP2B6, CYP3A5, and CYP2C19 Genetic Polymorphisms With Sibutramine Pharmacokinetics in Healthy Korean Subjects Clinical Pharmacology & Therapeutics 86, 511 (November 2009). doi:10.1038/clpt.2009.145 Authors: K A Kim, W K Song & J Y Park

Pharmacokinetic Study of Pegylated Liposomal CKD-602 (S-CKD602) in Patients With Advanced Malignancies

Pharmacokinetic Study of Pegylated Liposomal CKD-602 (S-CKD602) in Patients With Advanced Malignancies Clinical Pharmacology & Therapeutics 86, 519 (November 2009). doi:10.1038/clpt.2009.141 Authors: W C Zamboni, S Strychor, L Maruca, S Ramalingam, B A Zamboni, H Wu, D M Friedland, R P Edwards, R G Stoller, C P Belani & R K Ramanathan

Effects of Selective Serotonin Reuptake Inhibitor Therapy on Endothelial Function and Inflammatory Markers in Patients With Coronary Heart Disease

Effects of Selective Serotonin Reuptake Inhibitor Therapy on Endothelial Function and Inflammatory Markers in Patients With Coronary Heart Disease Clinical Pharmacology & Therapeutics 86, 527 (November 2009). doi:10.1038/clpt.2009.121 Authors: C Pizzi, S Mancini, L Angeloni, F Fontana, L Manzoli & G M Costa

Hydrochlorothiazide and Atenolol Combination Antihypertensive Therapy: Effects of Drug Initiation Order

Hydrochlorothiazide and Atenolol Combination Antihypertensive Therapy: Effects of Drug Initiation Order Clinical Pharmacology & Therapeutics 86, 533 (November 2009). doi:10.1038/clpt.2009.101 Authors: J A Johnson, Y Gong, K R Bailey, R M Cooper-DeHoff, A B Chapman, S T Turner, G L Schwartz, K Campbell, S Schmidt, A L Beitelshees, E Boerwinkle & J G Gums

Potential Clinical and Economic Outcomes of CYP2C9 and VKORC1 Genotype-Guided Dosing in Patients Starting Warfarin Therapy

Potential Clinical and Economic Outcomes of CYP2C9 and VKORC1 Genotype-Guided Dosing in Patients Starting Warfarin Therapy Clinical Pharmacology & Therapeutics 86, 540 (November 2009). doi:10.1038/clpt.2009.104 Authors: J H S You, K K N Tsui, R S M Wong & G Cheng

Pharmacokinetic Studies in Hemodialysis Patients

Pharmacokinetic Studies in Hemodialysis Patients Clinical Pharmacology & Therapeutics 86, 548 (November 2009). doi:10.1038/clpt.2009.147 Authors: A J Atkinson & J G Umans

The Influence of Chronic Renal Failure on Drug Metabolism and Transport

The Influence of Chronic Renal Failure on Drug Metabolism and Transport Clinical Pharmacology & Therapeutics 86, 553 (November 2009). doi:10.1038/clpt.2009.163 Author: A W Dreisbach

Drug Development Perspective on Pharmacokinetic Studies of New Drugs in Patients With Renal Impairment

Drug Development Perspective on Pharmacokinetic Studies of New Drugs in Patients With Renal Impairment Clinical Pharmacology & Therapeutics 86, 557 (November 2009). doi:10.1038/clpt.2009.182 Authors: R L Lalonde & J A Wagner

The Impact of Continuous Renal Replacement Therapy on Drug Therapy

The Impact of Continuous Renal Replacement Therapy on Drug Therapy Clinical Pharmacology & Therapeutics 86, 562 (November 2009). doi:10.1038/clpt.2009.152 Author: G M Susla

Public Health Consequences of Chronic Kidney Disease

Public Health Consequences of Chronic Kidney Disease Clinical Pharmacology & Therapeutics 86, 566 (November 2009). doi:10.1038/clpt.2009.137 Author: D E Weiner