The metabolism of ondansetron

Abstract

The metabolism of ondansetron has been studied in rat, dog and man. In laboratory animals absorption of the compound across the gastrointestinal tract is rapid and extensive, but due to high first-pass metabolism, the oral systemic bioavailability is low (less than 10%). The high systemic clearance of ondansetron results in a very short half-life in rat and dog. The renal clearance of ondansetron is low, indicating that the major route of systemic clearance is by metabolism. Routes of excretion of drug-related material differ between laboratory animals and man - the major route in the rat and dog is via the bile, while in man the predominant route is via the urine. However, the routes of metabolism are qualitatively similar in all species, indicating that the species used in toxicological testing of ondansetron were appropriate.