THE TOLERABILITY AND PHARMACOKINETICS OF THE NOVEL ANTIMIGRAINE COMPOUND 311C90 IN HEALTHY MALE-VOLUNTEERS

1 311C90 is a novel and selective agonist at 5-HT1D receptors, with ce ntral and peripheral actions, currently in development for the acute o ral treatment of migraine. 2 The pharmacokinetic and tolerability prof iles of single oral doses from 1-50 mg 311C90 were investigated in 12 healthy male volunteers in a double-blind, placebo-controlled, dose-es calating study. 3 311C90 was well tolerated with most adverse experien ces of mild and transient nature. 4 Absorption was rapid with dose-ind ependent kinetics. Median t(max) was 2-4 h although 50-85% of eventual C-max was attained within 1 h. The t(1/2) was 2.5-3 h with a high app arent plasma clearance (CL/F > 2000 ml min(-1)) and apparent volume of distribution (V-z/F) of 400-500 l. 5 Three metabolites were detected in plasma and urine, one of which, the N-desmethyl metabolite, has 5-H T1D agonist activity. 6 311C90 showed no clinically significant effect s on blood pressure, heart rate, ECG or laboratory variables at any do se and demonstrated a tolerability and pharmacokinetic profile compati ble with an acute oral migraine treatment.