Ondansetron excretion

After either oral or intravenous administration of [ Cjondansetron to rats the majority (about 80 %) of the radioactive dose is voided in the faeces, the remainder of the dose being excreted in the urine. In the dog, faecal elimination accounts for about half of the dose and is independent of the route of administration. Evidence from animals with cannulated bile-ducts indicates that the major route of excretion is via the bile. In both species, less than 5 % of the dose is excreted unchanged in urine, suggesting that extensive metabolism of ondansetron occurs. 

The metabolites of ondansetron have been examined in urine and bile from rat and dog. The major pathways for metabolism of ondansetron are A-demethylation and hydroxylation Scheme 7.7). However, whereas A-de-methylation predominates in dog, this is only a minor metabolic route in rat. Hydroxylation may occur at the 6, 7 or 8 position in the carbazolone ring. Hydroxy metabolites of ondansetron are excreted predominantly as glucuronide or sulphate conjugates. Studies with immobilised glucuronyl-transferase (Heath, S.E., personal communication) have demonstrated that O- and A-glucuronidation of ondansetron metabolites may occur. 

Three agents are available ondansetron, granisetron, and dolasetron. The drugs have a long serum half-life of 4-9 hours and may be administered once or twice daily by oral or intravenous routes. The drugs undergo extensive hepatic metabolism and are eliminated by renal and hepatic excretion. However, dose reduction is not required in geriatric patients or patients with renal insufficiency. For patients with hepatic insufficiency, dose reduction may be required with ondansetron. 

Ondansetron is 70-76% protein-bound. It is metabolized by the hepatic cytochrome P450 and excreted in the urine and feces. Less than 10% of the dose is unchanged in the urine. Its half-life is 5.7 hours... 

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