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The clinical pharmacokinetics of zolmitriptan.
Cephalalgia : An International Journal of Headache 1997 October
Zolmitriptan (Zomig, formerly 311C90) is a novel, oral, acute treatment for migraine. In healthy volunteers it is rapidly and extensively absorbed and has favorable oral bioavailability (approximately 40%) which is not affected by concomitant food intake. On average, 75% of its eventual Cmax is achieved within 1 h of dosing. Plasma concentrations are sustained for 4 to 6 h after dosing with single or multiple peaks in the plasma concentration-time profile, reflecting continued absorption down the gastrointestinal tract. The pharmacokinetics of zolmitriptan indicate dose proportionality over the dose range of 2.5 to 50 mg and there are no significant changes on multiple dosing. Zolmitriptan is cleared by metabolism followed by urinary excretion of the metabolites. There are three major metabolites, one of which, the N-desmethyl metabolite, is active as a 5HT1D agonist and has mean plasma concentrations approximately two thirds those of the parent compound. The other two metabolites, the N-oxide and indoleacetic acid, are inactive. The elimination half lives of zolmitriptan and its metabolites are similar, approximately 3 h. Zolmitriptan and its active metabolite are minimally protein bound in the plasma (approximately 25%). In migraine patients, plasma concentrations of zolmitriptan and its metabolites are lower during a migraine attack than outside an attack. In summary, the pharmacokinetics of zolmitriptan are simple, predictable and appropriate to an acute oral treatment for migraine.
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