Drug Metabolites in Safety Testing

doi:10.1006/taap.2002.9440

Toxicology and Applied Pharmacology

Volume 182, Issue 3, 1 August 2002, Pages 188-196

https://doi.org/10.1006/taap.2002.9440 Get rights and content

Abstract

This report summarizes the deliberations of a multidisciplinary committee, sponsored by the Pharmaceutical Research and Manufacturers of America, on current “best practices” within the U.S. pharmaceutical industry in assessing the role of drug metabolites as potential mediators of the toxicity of new drug products. Input to the document was obtained from numerous sources, including members of the pharmaceutical industry, academic investigators, and representatives of regulatory agencies who attended a workshop on the subject in November 2000. The overall goal of the paper is to define practical and scientifically based approaches to the use of metabolite data that address contemporary issues in the safety evaluation of drug candidates. Although there remains a lack of consensus on how best to deal with several aspects of this complex subject, this paper raises a number of points to consider, which emphasize the need to treat drug metabolite issues on a case-by-case basis. It is hoped that the discussion will promote continued dialog among industrial scientists and regulators charged with ensuring the clinical safety of new therapeutic agents.

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Contemporary Issues in ToxicologyDrug Metabolites in Safety Testing

Abstract

Mass spectrometry in the analysis of glutathione conjugates

Biol. Mass Spectrom.

Considerations in the design of toxicokinetic programs

Toxicol. Pathol.

Toxicokinetic challenges in the pharmaceutical industry

Toxicol. Pathol.

Pharmacogenomics: Translating functional genomics into rational therapeutics

Science

Properties of acyl glucuronides: Implications for studies of the pharmacokinetics and metabolism of acidic drugs

Drug Metab. Rev.

Tissue distribution and interindividual variation in human UDP-glucuronosyltransferase activity: Relationship between UGT1A1 promoter genotype and variability in a liver bank

Pharmacogenetics

Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics

Biochem. J.

Toxicokinetics: Its significance and practical problems

J. Toxicol. Sci.

Contemporary Issues in Toxicology
Drug Metabolites in Safety Testing