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.


CONCLUSIONS
Pharmacokinetic parameters of zolmitriptan were similar between Caucasian and Japanese volunteers.
Clinical Pharmacology Unit, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. roger.yates@astrazeneca.com
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Yates
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Tateno
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Nairn
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Ikegami
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Dane
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Kemp
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D017366:Serotonin Receptor Agonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012907:Smoking; D014363:Tryptamines; D044465:White People
D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan