Reactions and enzymes in the metabolism of drugs and other xenobiotics.
In this article, we offer an overview of the compared quantitative importance of biotransformation reactions in the metabolism of drugs and other xenobiotics, based on a meta-analysis of current research interests. Also, we assess the relative significance the enzyme (super)families or categories catalysing these reactions. We put the facts unveiled by the analysis into a drug discovery context and draw some implications. The results confirm the primary role of cytochrome P450-catalysed oxidations and UDP-glucuronosyl-catalysed glucuronidations, but they also document the marked significance of several other reactions. Thus, there is a need for several drug discovery scientists to better grasp the variety of drug metabolism reactions and enzymes and their consequences.
Service of Pharmacy, Lausanne University Hospital, Switzerland. Bernard.Testa@chuv.ch
Bernard
B
Testa
Alessandro
A
Pedretti
Giulio
G
Vistoli
D000818:Animals; D001669:Biochemical Phenomena; D055808:Drug Discovery; D064420:Drug-Related Side Effects and Adverse Reactions; D004798:Enzymes / Q000145:classification / Q000378:metabolism*; D006801:Humans; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity
D004798:Enzymes; D004364:Pharmaceutical Preparations; D015262:Xenobiotics