Pharmacokinetics and tolerability of oral rizatriptan in healthy male and female volunteers

Aims The pharmacokinetics and dose proportionality of rizatriptan single or al doses from 2.5 to 15 mg administered as solutions to healthy volunteers were studied. Methods In a randomized, crossover study with four periods, twenty-four hea lthy volunteers (12 males and 12 females) took single oral doses of 2.5, 5, 10, and 15 mg rizatriptan in Periods 1-4. In a fifth period, subjects rece ived 4 mg intravenous (i.v.) rizatriptan as a reference. Plasma and urine r izatriptan concentrations were determined at several timepoints/intervals f or 12 and 24 h, respectively. Results The arithmetic mean AUC values following single oral doses of 2.5, 5, 10, and 15-mg rizatriptan were 16, 33, 72, and 127 ng ml(-1) h, respecti vely, in males; and 19, 42, 97, and 161 ng ml(-1) h, respectively, in femal es. The overall bioavailability (F) of rizatriptan was similar to 40% in ma les. Following the 4 mg reference i.v. dose, the apparent plasma clearance (CL) and renal clearance (CL,) were 1042 and 225ml min(-1), respectively, i n males; and 821 and 174 mi min(-1), respectively, in females. Conclusions The disposition kinetics of oral rizatriptan were linear for do ses of 2.5-10 mg in males, and for doses of 2.5-5 mg in females. However, t he degree of nonlinearity for higher doses was minor for both genders. The plasma concentrations of rizatriptan were slightly greater in women compare d to men but the difference was not considered to be clinically meaningful. Also, the clearance of rizatriptan appeared to be mainly nonrenal.