PHARMACOKINETICS AND PHARMACODYNAMICS OF AVITRIPTAN IN PATIENTS WITH MIGRAINE AFTER ORAL DOSING

Avitriptan (BMS-180048) is a 5-HT1-like receptor agonist for the treat ment of migraine. This double-blind, placebo-controlled, randomized, p arallel-group study evaluated the pharmacokinetics, safety, and prelim inary efficacy of avitriptan in patients with migraine during migraino us and pain-free states. Patients met the IHS criteria for migraine wi th or without aura and suffered one to six migraines per month for at least 1 year. Patients in a clinic experiencing a migraine headache re ceived avitriptan 75 mg, 150 mg, or 200 mg or matching placebo capsule s. Blood samples were obtained before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, and 6 hours after dosing. Headache intensity was rated b efore and up to 6 hours after dosing. Seven to 30 days after the incli nic treatment, patients returned in a pain-free state for the same stu dy medication. All pharmacokinetic and safety measures were repeated. Forty-eight patients (9 men and 39 women) participated. Peak plasma co ncentrations of avitriptan were achieved 1 to 2 hours following dosing in migraine and pain-free states for all doses. The pharmacokinetics of avitriptan were proportional to dose during a migraine attack over the 75- to 200-mg dose range. The 150- and 200-mg doses of avitriptan demonstrated a greater decrease in headache intensity scores at 2 hour s postdose. The most common adverse event was paresthesia. Thus, avitr iptan was rapidly absorbed, well tolerated, and demonstrated prelimina ry efficacy in this population.