Chapter 11 - Pathways of Drug Metabolism

Abstract

Publisher Summary This chapter discusses pathways of drug metabolism. The biochemical processes governing drug metabolism largely determine the duration of a drug's action, elimination, and toxicity. Phenobarbital typifies the drugs that are active when administered and then are converted to inactive and more polar metabolites in the liver. Pyrimidine nucleotides exemplify a class of pharmaceuticals designed to be biotransformed in the body from inactive to active cancer chemotherapeutic agents. Among the major enzyme systems affecting drug metabolism, cytochrome P450 monooxygenases are dominant. The action of various cytochrome P450 (CYP) isoforms is predictable in that there are several organic structural elements that are principal targets for metabolic transformations. Many aromatic drugs are hydroxylated either directly through asymmetrical oxygen transfer or through an unstable arene oxide intermediate. In humans, glucuronidation is a high-capacity pathway, sulfation is a low-capacity pathway, and acetylation exhibits high interindividual variability. The glucuronidation pathway often accounts for a major portion of drug metabolites that are found excreted in urine.