Drug metabolism and metabolite safety assessment in drug discovery and development.

abstract：INTRODUCTION:Telaprevir is one of the first direct-acting antiviral drugs approved for the treatment of the hepatitis C virus (HCV) genotype 1. Following its approval in 2011, new data regarding the pharmacokinetics and pharmacodynamics were reported, leading to important clinical applications. AREAS COVERED:This arti...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Rivero-Juarez A,Camacho A,Rivero A

更新日期：2015-07-01 00:00:00

abstract：:Hyperphosphatemia is recognized as a principal mineral disorder in chronic kidney disease (CKD) that leads to the development of secondary hyperparathyroidism. Recent data indicate that hyperphosphatemia is associated with accelerated cardiac calcification and increased mortality in patients with CKD. Control of serum...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Barton Pai A,Conner TA,McQuade CR

更新日期：2009-01-01 00:00:00

abstract：INTRODUCTION:Membrane transport proteins play a central role in regulating the disposition of endobiotics, dietary nutrients and environmental toxins. The inhibition of transporters by drugs has potential physiologic consequences. The full extent of the effect of drugs on the function of transporters is poorly understo...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Lepist EI,Ray AS

更新日期：2017-10-01 00:00:00

abstract：INTRODUCTION:Catechins of green tea extract (GTE) have been associated with the rare risk of hepatotoxicity in a few individuals. As GTE were coadministered with synthetic drugs in some hepatotoxicity cases, uncertainty emerged whether GTE are a risk factor of drug-induced liver injury (DILI). AREAS COVERED:Case repor...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Teschke R,Zhang L,Melzer L,Schulze J,Eickhoff A

更新日期：2014-12-01 00:00:00

abstract：OBJECTIVE:The objectives of this study are to characterize capsaicin glucuronidation using liver microsomes and to determine the contribution of individual UDP-glucuronosyltransferase (UGT) enzymes to hepatic glucuronidation of capsaicin. METHODS:The rates of glucuronidation were determined by incubating capsaicin wit...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Sun H,Wang H,Liu H,Zhang X,Wu B

更新日期：2014-10-01 00:00:00

abstract：:Introduction: Antiepileptic drugs (AEDs) are the cornerstone of treatment of patients with epilepsy, and there are presently 27 licensed AEDs making AEDs among the most common medications for which therapeutic drug monitoring (TDM) is performed. The aim of this review is to provide an overview of the current evidence ...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Johannessen Landmark C,Johannessen SI,Patsalos PN

更新日期：2020-03-01 00:00:00

abstract：:Three first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury ranges from a mild to severe form, and the associated mortality cases are not rare. The major drug-metabolizing enzyme of isoniazid is N-acetyl...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Huang YS

更新日期：2007-02-01 00:00:00

abstract：INTRODUCTION:Idiosyncratic drug-induced agranulocytosis (IDIAG) is a life-threatening adverse reaction characterized by an absolute neutrophil count < 500 cells/μl of blood. It shares many of the characteristics of other idiosyncratic drug reactions (IDRs), and this presumably reflects mechanistic similarities. AREAS ...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Johnston A,Uetrecht J

更新日期：2015-02-01 00:00:00

abstract：INTRODUCTION:Treatments for hepatitis C virus (HCV) infection have advanced rapidly in the last decade. Pegylated interferon alpha 2a (PEG-IFN alpha 2a) alone, in combination with ribavirin and with or without direct acting antivirals (DAAs) is modestly effective in the treatment of chronic HCV infection. Areas covered...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Maughan A,Ogbuagu O

更新日期：2018-02-01 00:00:00

abstract：:The pharmaceutical relevance of proton-coupled peptide transporters is currently under intense investigation in many laboratories. Studies have shown that these membrane proteins, expressed in intestine, kidney, choroid plexus and other tissues, accept many peptidomimetic drugs and prodrugs as substrates. The focus of...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Brandsch M

更新日期：2009-08-01 00:00:00

abstract：INTRODUCTION:Pharmacokinetic and pharmacodynamic drug interactions (DIs) can occur between antiepileptics (AEDs) and second-generation antipsychotics (SGAPs). Some AED and SGAP pharmacodynamic mechanisms are poorly understood. AED-SGAP combinations are used for treating comorbid illnesses or increasing efficacy, partic...

journal_title：Expert opinion on drug metabolism & toxicology

authors： de Leon J,Santoro V,D'Arrigo C,Spina E

更新日期：2012-03-01 00:00:00

abstract：INTRODUCTION:Adverse drug reactions with an immune pathogenesis are a problem in the clinic and an impediment to drug development. T lymphocytes are believed to play a role in the pathogenesis; however, the nature of the drug interaction with immune receptors remains an area of debate. AREAS COVERED:This article revie...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Sullivan A,Gibson A,Park BK,Naisbitt DJ

更新日期：2015-03-01 00:00:00

abstract：INTRODUCTION:Short- and long-acting β agonists (SABA and LABA) are bronchodilators for treating asthma. Bronchodilator response (BDR) is quantified by measuring air expired in the first second during a forced expiratory maneuver, prior to and following inhalation of SABA. BDR has been associated with a significant degr...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Lima JJ

更新日期：2014-09-01 00:00:00

abstract：BACKGROUND:Cytochrome P450 2E1 (CYP2E1) plays a central role in the metabolism and metabolic activation of a large number of small, mostly xenobiotic compounds. These qualities distinguish CYP2E1 from traditional enzymes and pose significant challenges to understanding the role and consequences of CYP2E1-mediated metab...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Miller GP

更新日期：2008-08-01 00:00:00

abstract：INTRODUCTION:Recent advances in molecular biology have enabled personalized cancer therapies with molecularly targeted agents (MTAs), which offer a promising future for cancer therapy. Dynamic modeling and simulation (M&S) is a powerful mathematical approach linking drug exposures to pharmacological responses, providin...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Yamazaki S,Spilker ME,Vicini P

更新日期：2016-01-01 00:00:00

abstract：INTRODUCTION:Various trials have attempted to develop gene expression profiles (GEPs) that may provide a better predictor of clinical outcome over traditional clinicopathological criteria. AREAS COVERED:The review focuses on two main areas: trials examining chemotherapy-induced GEP changes pre- and post-treatment, and...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Tan SH,Lee SC

更新日期：2012-09-01 00:00:00

abstract：INTRODUCTION:The prevalence of obesity and associated co-morbid conditions is increasing globally. Physiological changes accompanying obesity are likely to result in altered drug pharmacokinetics; however, there is paucity of information on how to best dose adjust for the obese. AREAS COVERED:This review presents mate...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Morrish GA,Pai MP,Green B

更新日期：2011-06-01 00:00:00

abstract：INTRODUCTION:For orally administered drugs, their intestinal absorption and hepatic metabolism are key players for determining a drug's systemic bioavailability and thus therapeutic effect. Drug absorption and metabolism are both complicated processes, with many physicochemical and physiological factors involved. Under...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Alqahtani S,Mohamed LA,Kaddoumi A

更新日期：2013-10-01 00:00:00

abstract：:It has increasingly been recognized that few molecules move across the cell membrane without the assistance of transporter proteins. Large superfamilies of transporter proteins have been identified in every living cell, including microorganisms and mitochondria. This report reviews the role of transporters in physiolo...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Lee EJ,Lean CB,Limenta LM

更新日期：2009-11-01 00:00:00

abstract：:There is wide inter-individual variability in the pharmacokinetics, pharmacodynamics and tolerance of anticancer drugs. Recent evidence suggests that there is even greater variability between individuals of different ethnicity. Allelic variants of genes encoding drug metabolising enzymes are expressed with different i...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Phan VH,Moore MM,McLachlan AJ,Piquette-Miller M,Xu H,Clarke SJ

更新日期：2009-03-01 00:00:00

abstract：INTRODUCTION:If a drug is found to be an inducer of hepatic drug metabolizing enzymes via activation of nuclear receptors such as pregnane X receptor (PXR) or constitutive androstane receptor (CAR), it is likely that drug transporters regulated through these same receptors will be induced as well. This review highlight...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Amacher DE

更新日期：2016-12-01 00:00:00

abstract：INTRODUCTION:Co-medication, gene polymorphisms and co-morbidity are main causes for high variability in expression and function of the CYP3A isoenzymes. Pharmacokinetic variability is a major source of interindividual variability of drug effect and response of CYP3A substrates. While CYP3A genotyping is of limited use,...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Hohmann N,Haefeli WE,Mikus G

更新日期：2016-05-01 00:00:00

abstract：INTRODUCTION:Sumatriptan was developed more than 20 years ago as a 5-HT1B/1D receptor agonist, the first drug in a new class of specific anti-migraine drugs, the triptans. A large amount of information and experience has been gained from the clinical trials undertaken as well the various formulations of sumatriptan use...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Tfelt-Hansen P,Hougaard A

更新日期：2013-01-01 00:00:00

abstract：INTRODUCTION:Patients with gout often have comorbid conditions such as renal failure, cardiovascular disease and metabolic syndrome. The presence and required treatment of these conditions can make the treatment of gout challenging. Knowledge of the pharmacokinetics of the available drugs for the management of gout is ...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Richette P,Frazier A,Bardin T

更新日期：2014-07-01 00:00:00

abstract：:Pathologists play a central role in the recognition and prevention of drug-induced toxicity. Pathologists engaged in clinical practice must identify a pattern of histological lesions that are interpreted in concert with a variety of clinical data to determine the probability of drug-induced toxicity versus background ...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Cullen JM,Miller RT

更新日期：2006-04-01 00:00:00

abstract：BACKGROUND:Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also have their limitations...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Gao B,Klumpen HJ,Gurney H

更新日期：2008-10-01 00:00:00

abstract：INTRODUCTION:The N-acetylation polymorphism has been the subject of comprehensive reviews describing the role of arylamine N-acetyltransferase 2 (NAT2) in the metabolism of numerous aromatic amine and hydrazine drugs. AREAS COVERED:We describe and review data that more clearly defines the effects of NAT2 haplotypes an...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Hein DW,Millner LM

更新日期：2021-01-01 00:00:00

abstract：INTRODUCTION:Therapeutic hypothermia is being employed clinically due to its neuro-protective benefits. Both critical illness and therapeutic hypothermia significantly affect drug disposition, potentially contributing to drug-therapy and drug-disease interactions. Currently, there is limited information on the known al...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Zhou J,Poloyac SM

更新日期：2011-07-01 00:00:00

abstract：INTRODUCTION:Piperine has various pharmacological effects and can modulate the functional activity of metabolic enzymes and drug transporters. Consequently, there is a great interest in the application of piperine as an alternative medicine or bioavailability enhancer. Areas covered: This review deals with the effects ...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Lee SH,Kim HY,Back SY,Han HK

更新日期：2018-01-01 00:00:00

abstract：:Luminogenic cytochrome P450 (CYP) assays couple CYP enzyme activity to firefly luciferase luminescence in a technology called P450-Glo(TM) (Promega). Luminogenic substrates are used in assays of human CYP1A1, -1A2, -1B1, -2C8, -2C9, -2C19, -2D6, -2J2, -3A4, -3A7, -4A11, -4F3B, -4F12 and -19. The assays detect dose-dep...

journal_title：Expert opinion on drug metabolism & toxicology

authors： Cali JJ,Ma D,Sobol M,Simpson DJ,Frackman S,Good TD,Daily WJ,Liu D

更新日期：2006-08-01 00:00:00