Lack of effect of ondansetron on the pharmacokinetics and analgesic effects of morphine and metabolites after single-dose morphine administration in healthy volunteers

Aims The purpose of this investigation was to study the influence of ondans etron on the single-dose pharmacokinetics and the analgesic effects elicite d by morphine and the 3- and 6-glucuronide metabolites of morphine in healt hy volunteers. Methods This was a randomized, double-blind, placebo-controlled, two-way cr ossover study in which six male and six female subjects were administered a single 10 mg intravenous dose of morphine sulphate, followed 30 min later by a single 16 mg intravenous dose of ondansetron hydrochloride or placebo. Serum and urine concentrations of morphine, morphine-3-glucuronide (M3G) a nd morphine-6-glucuronide (M6G) samples were quantified over 48 h using hig h performance liquid chromatography with detection by mass spectrometry. An algesia was assessed in the volunteers with a contact thermode device to pr ovide a thermal pain stimulus. Four analgesic response variables were measu red including thermal pain threshold, thermal pain tolerance, temporal summ ation of pain and mood state. Results The two treatments appeared to be equivalent based on the 90% confi dence intervals (0.6, 1.67) of the least squares means ratio. All least squ ares means ratio confidence intervals for each parameter, for each analyte fell within the specified range, demonstrating a lack of an interaction. Conclusions The results of this study suggest that administration of ondans etron (16 mg i.v.) does not alter the pharmacokinetics of morphine and its 3- or 6-glucuronide metabolites to a clinically significant extent, nor doe s it affect the overall analgesic response to morphine as measured by the c ontact thermode system.