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Approved Drugs (approved + drug)
Selected AbstractsIs there an experimental basis for the development of ischaemic colitis as a result of 5-HT3 antagonist treatment?NEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2007M. Camilleri Abstract, 5-HT3 antagonists are effective treatments for chemotherapy-induced emesis and diarrhoea and urgency and pain associated with irritable bowel syndrome. Reports of ischaemic colitis led to restricted use of the approved drug, alosetron. This article briefly reviews the controversial information from epidemiology and adverse reaction reports and addresses the experimental basis for the development of ischaemic colitis as a result of 5-HT3 antagonist treatment. The author reviews the potential factors based involved in the ischaemic colitis and ways in which this class of compound may influence those factors based on experimental evidence, including the literature on any vascular effects of these agents. Finally, the article addresses the theoretical basis for the constipation as a predisposing factor for the development of ischaemic colitis. The evidence reviewed suggests that further studies are needed to explore the principles to prove or disprove the association. [source] Salting-out assisted liquid/liquid extraction with acetonitrile: a new high throughput sample preparation technique for good laboratory practice bioanalysis using liquid chromatography,mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 4 2009Jun Zhang Abstract Acetonitrile, an organic solvent miscible with aqueous phase, has seen thousands of publications in the literature as an efficient deproteinization reagent. The use of acetonitrile for liquid,liquid extraction (LLE), however, has seen very limited application due to its miscibility with aqueous phase. The interest in LLE with acetonitrile has been pursued and reported in the literature by significantly lowering the temperature of the mixture or increasing the salt concentration in the mixture of acetonitrile and aqueous phase, resulting in the separation of the acetonitrile phase from aqueous phase, as observed in conventional LLE. However, very limited application of these methods has been reported. The throughput was limited. In this report, we report a new sample preparation technique, salting-out assisted liquid,liquid extraction with acetonitrile, for high-thoughput good laboratory practice sample analysis using LCMS, Two compounds from an approved drug, Kaletraź, were used to demonstrate the extractability of drugs from human plasma matrix. Magnesium sulfate was used as the salting-out reagent. Extracts were diluted and then injected into a reversed phase LC-MS/MS system directly. One 96-well plate was extracted with this new approach to evaluate multiple parameters of a good laboratory practice analytical method. Results indicate that the method is rapid, reliable and suitable for regulated bioanalysis. With minimal modification, this approach has been used for high-throughput good laboratory practice analysis of a number of compounds under development at Abbott. Copyright © 2008 John Wiley & Sons, Ltd. [source] Population pharmacokinetics of intravenously and orally administered docetaxel with or without co-administration of ritonavir in patients with advanced cancerBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2010Stijn L. W. Koolen WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Docetaxel is an approved drug for the treatment of cancer of various primary origins. , An oral docetaxel regimen is warranted because of patient convenience and the opportunity to investigate more schedule intensive treatment regimens. , Co-administration of ritonavir significantly enhanced the apparent oral bioavailability of docetaxel. WHAT THIS STUDY ADDS , This study demonstrates that ritonavir increased the absorption of docetaxel after oral administration. , Furthermore, we showed that the clearance of docetaxel was inhibited in a concentration dependent manner. , The developed model will be used for further development of an oral docetaxel regimen. AIM Docetaxel has a low oral bioavailability due to affinity for P-glycoprotein and cytochrome P450 (CYP) 3A4 enzymes. Inhibition of the CYP3A4 enzymes by ritonavir resulted in increased oral bioavailability. The aim of this study was to develop a population pharmacokinetic (PK) model and to evaluate and quantify the influence of ritonavir on the PK of docetaxel. METHODS Data from two clinical trials were included in the data analysis, in which docetaxel (75 mg m,2 or 100 mg) had been administered intravenously or orally (10 mg or 100 mg) with or without co-administration of oral ritonavir (100 mg). Population modelling was performed using non-linear mixed effects modelling. A three-compartment model was used to describe the i.v. data. PK data after oral administration, with or without co-administration of ritonavir, were incorporated into the model. RESULTS Gut bioavailability of docetaxel increased approximately two-fold from 19 to 39% (CV 13%) with ritonavir co-administration. The hepatic extraction ratio and the elimination rate of docetaxel were best described by estimating the intrinsic clearance. Ritonavir was found to inhibit in a concentration dependent manner the intrinsic clearance of docetaxel, which was described by an inhibition constant of 0.028 ”g ml,1 (CV 36%). A maximum inhibition of docetaxel clearance of more then 90% was reached. CONCLUSIONS A PK model describing both the PK of orally and intravenously administered docetaxel in combination with ritonavir, was successfully developed. Co-administration of ritonavir lead to increased oral absorption and reduced elimination rate of docetaxel. [source] Preclinical and clinical pharmacology of alcohol dependenceFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2007Sophie Tambour Abstract In recent years, advances in neuroscience led to the development of new medications to treat alcohol dependence and especially to prevent alcohol relapse after detoxification. Whereas the earliest medications against alcohol dependence were fortuitously discovered, recently developed drugs are increasingly based on alcohol's neurobiological mechanisms of action. This review discusses the most recent developments in alcohol pharmacotherapy and emphasizes the neurobiological basis of anti-alcohol medications. There are currently three approved drugs for the treatment of alcohol dependence with quite different mechanisms of action. Disulfiram is an inhibitor of the enzyme aldehyde dehydrogenase and acts as an alcohol-deterrent drug. Naltrexone, an opiate antagonist, reduces alcohol craving and relapse in heavy drinking, probably via a modulation of the mesolimbic dopamine activity. Finally, acamprosate helps maintaining alcohol abstinence, probably through a normalization of the chronic alcohol-induced hyperglutamatergic state. In addition to these approved medications, many other drugs have been suggested for preventing alcohol consumption on the basis of preclinical studies. Some of these drugs remain promising, whereas others have produced disappointing results in preliminary clinical studies. These new drugs in the field of alcohol pharmacotherapy are also discussed, together with their mechanisms of action. [source] Outline of the Japanese Guidelines for the Management of Stroke 2004 and subsequent revisionINTERNATIONAL JOURNAL OF STROKE, Issue 1 2008Yukito Shinohara During its preparation, 106 stroke specialists from these societies checked and rated more than 110,000 publications from all over the world, including Japan. We thought it important to develop specific guidelines for Japanese patients, because there are race differences, because some of the approved drugs in Japan are different from those in other counties, and because reports published in Japanese have not been taken into consideration in the development of western guidelines. We also added the Japanese guidelines for use of t-PA in this outline, because there are some differences (e.g., in volume of t-PA) from the guidelines of western countries. Here, we present an outline the Japanese Guidelines for the Management of Stroke 2004 in response to requests, although some updating is already needed. The first revision of the guidelines is expected to be completed in 2008. [source] Current treatment strategies for pulmonary arterial hypertensionJOURNAL OF INTERNAL MEDICINE, Issue 3 2005S. H. LEE Abstract., Lee SH, Rubin LJ (University of California, San Diego, La Jolla, CA, USA). Current treatment strategies for pulmonary arterial hypertension (Review). J Intern Med 2005; 258: 199,215. Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. Although there is no cure for PAH, newer medical therapies have been shown to improve a variety of clinically relevant end-points including survival, exercise tolerance, functional class, haemodynamics, echocardiographic parameters and quality of life measures. Since the introduction of continuous intravenous prostacyclin, the treatment armamentarium of approved drugs for PAH has expanded to include prostacyclin analogues with differing routes of administration, a dual endothelin receptor antagonist, and a phosphodiesterase-5 inhibitor. Selective endothelin-A receptor antagonists have shown promise in clinical trials and are likely to be added to the list of options. As the number of medications available for PAH continues to increase, treatment decisions regarding first-line therapy, combination treatments, and add-on strategies are becoming more complex. This article reviews the current treatments strategies for PAH and provides guidelines for its management. [source] Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiologyBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2010Adam L. VanWert Abstract Our understanding of the mechanisms behind inter- and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient- and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||