The clinical pharmacology of ondansetron.

Ondansetron, a 5-HT3 antagonist proposed for use in the treatment of chemotherapy-induced emesis, was first given to man in 1984 and in the 4 years subsequent to this, the drug was given to more than 220 different healthy volunteers. In pharmacodynamic studies, there was evidence to suggest that ondansetron was gastroprokinetic but reduced transit time through the small bowel. Ondansetron was of no benefit in a model of motion sickness. The pharmacokinetics of ondansetron have been defined in volunteers using intravenous and oral dosage regimens proposed for the clinic. Ondansetron had a terminal plasma half-life of 3.0-3.5 h and plasma clearance (principally metabolic) of the order of 600 ml/min, and there was no evidence of accumulation at steady state. The absolute oral bioavailability of ondansetron was 59%. Metabolic studies showed the drug to be excreted predominantly in urine and faeces, with a metabolite profile in urine similar to that seen in the animal species used for toxicological testing. Ondansetron is both safe and well tolerated at daily doses of up to 64 mg given to volunteers.