Pharmacokinetic and pharmacodynamic aspects of the interaction between clazosentan and nimodipine in healthy subjects

Background. The objective of this study was firstly to evaluate a possible pharmacodynamic interaction between clazosentan, an endothelin receptor antagonist, and nimodipine in healthy subjects. Secondly, the objective was to assess the pharmacokinetics, safety, and tolerability of clazosentan co-administered with nimodipine. Method. The pharmacodynamic assessment consisted of frequent recording of vital signs. For pharmacokinetic purposes, blood samples were taken at different time points during and following the infusion of 0.2 mg/kg/h clazosentan, which lasted for 6 h. Findings. In previous studies, clazosentan was shown to reduce blood pressure in healthy subjects. The present data confirm this observation but do not suggest that concomitant nimodipine amplified this decrease in blood pressure. In the presence of nimodipine, the geometric mean values (95% confidence interval) for clearance and volume of distribution of clazosentan were 37.7 (34.8, 40.9) L/h and 21.5 (17.4, 26.7) L, respectively, similar to previously reported numbers. Conclusions. Pharmacodynamic and pharmacokinetic data suggest that there was no interaction between clazosentan and nimodipine. The concomitant administration of clazosentan and nimodipine was safe and well tolerated.