Metabolism of Gyrase Inhibitors

Abstract

Since metabolites of gyrase inhibitors (including the quinolones) may contribute to or even determine the occurrence of adverse effects or interactions with other drugs, an understanding of even minor metabolic pathways is important. The extent of metabolism can be estimated by determination of the renal and nonrenal clearance of drug and by measurement of excretion of drug labeled with 14C. The principal metabolic pathways of gyrase inhibitors are piperazine ring-based reactions (formation of oxo-compounds, N-oxides, demethylation products where applicable, or ring cleavage with or without subsequent metabolic conversions) and acyl-glucuronidation at the carboxy group of the nucleus. The measurement of metabolites in plasma represents the formation, distribution, and elimination of metabolites in the body. Sensitive techniques have been developed for measuring the penetration of metabolites into fluid and tissue, and studies have been made of the metabolism of gyrase inhibitors in patients with renal failure or hepatic dysfunction. Factors that affect metabolism of gyrase inhibitors include smoking, gender, genetically determined metabolic competency, and dosing schedule.