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.
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. A pharmacokinetic study with intravenous granisetron HCl in patients with hepatic impairment due to neoplastic liver involvement showed that total clearance was approximately halved compared to patients without hepatic impairment. Given the wide variability in pharmacokinetic parameters noted in patients and the good tolerance of doses well above the recommended 1.0 mg b.i.d. dose, dosage adjustment in patients with possible hepatic functional impairment is not necessary. The pharmacokinetics of granisetron has not been adequately studied in children. No vomiting and no moderate or severe nausea.