The pharmacokinetics of intravenous ondansetron in patients with hepatic impairment.

Abstract

The pharmacokinetics of the 5-HT3 receptor antagonist ondansetron were investigated following a single 8 mg intravenous dose given over 5 min in 19 patients with varying degrees of hepatic impairment and in six young healthy subjects. In comparison with the healthy controls, the patients with severe hepatic impairment had a lower mean plasma clearance (96 ml min-1 vs 478 ml min-1) and increased AUC (1383 ng ml-1 h vs 279 ng ml-1 h) and t1/2 (21 h vs 3.6 h). These differences were all statistically significant (P < 0.001). The corresponding values for patients with mild or moderate hepatic impairment fell between these extremes. Vss was greater in all patient groups than the control group, but the magnitude of the change was smaller than for the other parameters and did not reflect the increasing severity of hepatic impairment. There were no significant changes in Cmax. There were no drug-related adverse events in the patients studied. It is recommended that the dosing frequency of ondansetron be limited to once daily in patients with severe hepatic impairment.