Lack of a Pharmacokinetic/Pharmacodynamic Interaction Between Nimodipine and Tirilazad Mesylate in Healthy Volunteers

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Abstract
The potential interaction between tirilazad mesylate, a membrane lipid peroxidation inhibitor, and nimodipine, a calcium-channel antagonist, was assessed in 12 healthy male volunteers. Subjects received 60 mg nimodipine orally, 2.0 mg/kg tirilazad mesylate as a 10-minute intravenous infusion, and a combination of the two treatments according to a balanced 3-way crossover design. No significant effects of nimodipine on tirilazad mesylate pharmacokinetic parameters were observed (P > .05). Values for tirilazad mesylate clearance (34.9 +/- 8.96 L/hr) and half-life (29 +/- 7.83 hr) were consistent with previous studies. Nimodipine pharmacokinetic parameters exhibited substantial variability, and mean AUC was approximately 25% below the range of previously published values. However, no significant differences in nimodipine pharmacokinetics were observed between treatments. Nimodipine administration increased heart rate slightly without a change in blood pressure, which was not observed after tirilazad administration and was not altered when tirilazad and nimodipine were coadministered. Thus, no significant interaction between tirilazad mesylate and nimodipine is detectable after single-dose administration.