Cytochrome P450s and other enzymes in drug metabolism and toxicity
Journal Title: The AAPS Journal - Year 2006, Vol 8, Issue 1
Abstract
The cytochrome P450 (P450) enzymes are the major catalysts involved in the metabolism of drugs. bioavailability and toxicity are 2 of the most common barriers in drug development today, and P450 and the conjugation enzymes can influence these effects. The toxicity of drugs can be considered in 5 contexts: on-target toxicity, hypersensitivity and immunological reactions, off-target pharmacology, bioactivation to reactive intermediates, and idiosyncratic drug reactions. the chemistry of bioactivation is reasonably well understood, but the mechanisms underlying biological responses are not. In the article we consider what fraction of drug toxicity actually involves metabolism, and we examine how species and human interindividual variations affect pharmacokinetics and toxicity.
Authors and Affiliations
F. Peter Guengerich
Keywords
Related Articles
- EP ID EP681643
- DOI 10.1208/aapsj080112
- Views 81
- Downloads 0
International Guidelines for Bioequivalence of Locally Acting Orally Inhaled Drug Products: Similarities and Differences
The online version of this article (doi:10.1208/s12248-015-9733-9) contains supplementary material, which is available to authorized users.
Epigenetic Modifications of Nrf2 by 3,3′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors
The online version of this article (doi:10.1208/s12248-013-9493-3) contains supplementary material, which is available to authorized users.
Biological Products for the Treatment of Psoriasis: Therapeutic Targets, Pharmacodynamics and Disease-Drug-Drug Interaction Implications
Psoriasis is a chronic inflammatory skin disease condition that involves altered expression of a broad spectrum of proinflammatory cytokines which are associated with activation of T cells and proliferation of keratinocy...
A survey of population analysis methods and software for complex pharmacokinetic and pharmacodynamic models with examples
An overview is provided of the present population analysis methods and an assessment of which software packages are most appropriate for various PK/PD modeling problems. Four PK/PD example problems were solved using the...
Bioanalytical Approaches to Quantify “Total” and “Free” Therapeutic Antibodies and Their Targets: Technical Challenges and PK/PD Applications Over the Course of Drug Development
The predominant driver of bioanalysis in supporting drug development is the intended use of the data. Ligand-binding assays (LBA) are widely used for the analysis of protein biotherapeutics and target ligands (L) to supp...