Safety, tolerance, and pharmacokinetics of subcutaneous Imitrex were first evaluated in U.S. clinical trials in 1988. An ascending-dose design was employed utilizing a placebo control with each dose level of Imitrex (1, 2, 3, or 4 mg) (4). No serious adverse events were demonstrated in healthy male volunteers receiving up to the maximum dose (4 mg). The study protocol was therefore amended and doses up to 16mg SC were administered without serious adverse events. It was noted that the incidence of adverse events tended to increase with increasing dose.