Pharmacokinetics and hemodynamic effects of nisoldipine and its interaction with cimetidine.

Pharmacokinetics, diastolic blood pressure, and heart rate after oral and intravenous nisoldipine were studied in eight healthy subjects without and with cotreatment of cimetidine in a four-way crossover design. After intravenous infusion, elimination half-life (t1/2) was 4.0 +/- 2.3 hours, systemic clearance (CL) was 0.83 +/- 0.17 L/min, and volume of distribution was 1.6 +/- 0.6 L/kg. After oral nisoldipine, t1/2 was 3.8 +/- 1.3 hours and systemic availability was 3.9% +/- 3.5%. During cimetidine, t1/2 and CL were not different. Systemic availability increased to 5.7% +/- 2.8%. After all nisoldipine treatments a significant decrease in supine diastolic blood pressure (mean 10% to 16%) and increase in heart rate (mean 22% to 44%) were observed. Hemodynamic effects until 2 hours after nisoldipine administration could be fitted to a sigmoidal Emax model. At times after 2 hours a second effect peak was observed. Cimetidine inhibits the metabolism of nisoldipine but has no significant influence on hemodynamic parameters.