EFFECT OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS OF ZOLMITRIPTAN

Zolmitriptan an oral 5HT(1D) agonist for the acute treatment of migrai ne, is cleared from the systemic circulation mainly by hepatic metabol ism. Consequently, changes in hepatic function may result in changes i n the pharmacokinetics of zolmitriptan. This open, parallel-group stud y was conducted to compare the pharmacokinetics and tolerability of a single 10-mg dose of zolmitriptan in healthy subjects and patients wit h hepatic impairment. A fetal of 37 participants entered and completed the study, including 10 healthy volunteers, 11 patients with moderate hepatic impairment, 10 patients with severe hepatic impairment withou t ascites, and 6 patients with severe hepatic impairment with ascites. The metabolism of zolmitriptan was reduced in patients with severe he patic impairment compared with healthy subjects, resulting in higher p eak plasma concentrations (47%), increased exposure (226%), and prolon ged half-life (157%). The changes were similar in the presence and abs ence of as cites. Smaller changes were observed in patients with moder ate hepatic impairment. Plasma concentrations of the three major metab olites of zolmitriptan were reduced in the patients with hepatic impai rment. Patients with moderate hepatic impairment require no dosage adj ustment, but the recommended daily intake of zolmitriptan may need to be reduced in patients with severe hepatic impairment. Journal of Clin ical Pharmacology, 1998;38:694-701 (C) 1998 The American College of Cl inical Pharmacology.