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Four separate studies were conducted to examine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of eletriptan, a 5-HT1B/1D receptor agonist being developed for the treatment of migraines, after oral and intravenous administration. Fifty-five males received oral (1.5–30 mg or 30–120 mg) or intravenous (1.67–50 μg/kg or 50–102 μg/kg) eletriptan in four double- and single-blind, placebo-controlled, ascending-dose crossover studies. The maximum plasma concentration (Cmax) and area under the concentration curve (AUC) appeared linear over all dose ranges, with an apparent terminal half-life of 4 to 5 hours. Clearance and volume of distribution remained constant with dose. The time to first occurrence of Cmax (tmax) for oral eletriptan was approximately 1 hour and was unaffected by dose. Comparison of AUC values suggested an absolute bioavailability of approximately 50%. A linear PK/PD model, fitted to the data, predicted small, transient elevations in diastolic blood pressure following eletriptan doses ≥ 60 mg. These effects were considered unlikely to be clinically significant. Eletriptan was well tolerated, and treatment-related adverse events were mild to moderate and transient. These PK properties should result in eletriptan having a rapid onset and sustained duration of action in terms of migraine efficacy.