Bioequivalence and safety of subcutaneously and intramuscularly administrred dihydroergotamine in healthy volunteers

Abstract

The bioequivalence and safety of subcutaneous (SC) and intramuscular (IM) administration of dihydroergotamine were determined in 30 healthy male volunteers (18 to 32 years of age) by using a randomized, crossover, 2 × 2 Latin square design. Two one-sided t tests, conventional 90% confidence intervals (CI), and Westlake's 95% CI showed that SC administration of dihydroergotamine achieved values for area under the plasma concentration time curve (AUC), AUC 0–∞, peak plasma concentration, and time to peak plasma concentration equivalent to those obtained after IM administration. The most frequently reported adverse events were myalgia, nausea, lightheadedness, and headache. Myalgia and lightheadedness occurred slightly more frequently after SC administration, while nausea occurred slightly more frequently after IM administration. There was a total of four reports of injection site reactions, including burning sensation, ecchymosis, and thickening at the injection site, three of which were associated with SC administration. All adverse events reported during the study were of mild intensity and resolved without treatment. None of the subjects was withdrawn from the trial prematurely because of adverse events. There were no clinically significant posttreatment changes in the findings from the physical examination, electrocardiogram, or clinical laboratory testing. The findings indicate that SC administration of dihydroergotamine for the treatment of migraine is a viable alternative to IM administration and will offer patients an opportunity to self-administer dihydroergotamine at the onset of headache.