Drug Metabolism

This chapter is a detailed account of drug metabolism, prodrugs and related terminology that are critical knowledge base for pharmacist and pharmacy education. After study of this chapter, students will be able to: • Comprehend the fundamental concepts of drug metabolism • Describe the significance of drug metabolism • Identify key enzymes involved and the sites of drug metabolism • Explain phase I and phase II metabolic pathways, including: ♦ Phase I (Functionalization) - Oxidation of aromatic moieties, olefins, benzylic & allylic C atoms and α-C of C=O and C=N, aliphatic and alicyclic C, C-heteroatom system, C-N (N-dealkylation, Noxide formation, N-hydroxylation), C-O (O-dealkylation), C-S (S-dealkylation, Soxidation, desulfuration), alcohols and aldehydes, and miscellaneous oxidative reactions - Reduction of aldehydes and ketones, Nitro and azo compounds, and miscellaneous reductive metabolisms - Hydrolytic reactions of esters and amides, epoxides and arene oxides by epoxide hydrase ♦ Phase II (Conjugation) - Glucuronic acid conjugation, sulfate conjugation, glycine and other amino acid, glutathione or mercapturic acid, acetylation, methylation - Define and differentiate between prodrug, soft drug and antedrugs - Discuss metabolic routes of some individual drugs

Keywords: Antedrug, Conjugation, Drug interactions, Drug metabolism, Enterohepatic circulation, First pass effect, Phase I metabolism, Phase II metabolism, Prodrug, Soft drug.