Following single and multiple oral doses, granisetron HCl slowed colonic transit in normal volunteers. There was high inter and intrasubject variability noted in these studies. No difference in mean AUC was found between males and females, although males had a higher C max generally. Granisetron metabolism involves N-demethylation and aromatic ring oxidation followed by conjugation. Animal studies suggest that some of the metabolites may also have 5-HT 3 receptor antagonist activity.
Clearance is predominantly by hepatic metabolism.
In vitro liver microsomal studies show that granisetron's major route of metabolism is inhibited by ketoconazole, suggestive of metabolism mediated by the cytochrome P-450 3A subfamily. N.D. Not determine The effects of gender on the pharmacokinetics of oral granisetron HCl have not been studied. However, after intravenous infusion of granisetron HCl, no difference in mean AUC was found between males and females, although males had a higher C max generally. Granisetron metabolism involves N-demethylation and aromatic ring oxidation followed by conjugation. Animal studies suggest that some of the metabolites may also have 5-HT 3 receptor antagonist activity.