The pharmacokinetics of the antimigraine compound zolmitriptan in Japanese and Caucasian subjects

Background: Zolmitriptan is a 5HT(1B/1D) receptor agonist effective in the acute treatment of migraine. Clinical trials in the USA and Europe have demonstrated the optimal oral therapeutic dose to be 2.5 mg. The 2.5-mg oral tablet has recently been licensed in Japan. Objective: To compare the pharmacokinetics of zolmitriptan and its metabolites in Japanese and Caucasian subjects and evaluate the effect of gender on these pharmacokinetics in Japanese volunteers. Methods: In this open, parallel-group study, 30 Japanese and 30 Caucasian volunteers (20-45 years) received a single 2.5-mg zolmitriptan tablet in the fasting state. Blood samples were taken up to 15 h post-dose to determine plasma concentrations of zolmitriptan and its active metabolite, 183C91. Urinary excretion of zolmitriptan, 183C91 and the inactive N-oxide and indole acetic acid metabolites were measured over 24 h. Results: Japanese volunteers were, on average, smaller and lighter than Caucasian volunteers. Plasma-concentration profiles of zolmitriptan and 183C91 were similar in the two groups. Although geometric mean zolmitriptan and 183C91 area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C-max) were slightly higher in Japanese subjects (up to 20%), these differences were not considered to be of clinical relevance as the 90% confidence interval for the ratio of AUCs fell within pre-specified limits (0.67 to 1.5). Mean zolmitriptan and 183C91 half-lives were around 2.5 h for both populations. Urinary excretion of the four analytes was similar in Japanese and Caucasians. Plasma concentrations of zolmitriptan were higher in Japanese females than males (AUC 40% and C-max 29% higher), consistent with the results previously obtained in Caucasians. Conclusion: Pharmacokinetic parameters of zolmitriptan were similar between Caucasian and Japanese volunteers.