Pharmacokinetics, Bioavailability/Metabolism, and Hemodynamic Effects of the Calcium Channel Antagonist Nitrendipine

The pharmacokinetics, bioavailability, metabolism, and hemodynamic effects of the calcium channel antagonist nitrendipine were studied in six healthy volunteers. Using a stable isotope technique, drug absorption, bioavailability, and pharmacokinetics were determined in one experiment following simultaneous intravenous and oral administration. Terminal half-lives were on average 8.3 ± 3.2 h. Plasma clearance was 18.6 ± 3.6 ml/min/kg and nearly reached liver blood flow. Thus, after oral administration, the high extraction ratio of nitrendipine results in an absolute bioavailability of only 22.6 ± 6.7%, despite its almost complete absorption (88.4 ± 16.0%). A significant correlation between the various hemodynamic effects (blood pressure, peripheral blood flow, and peripheral vascular resistance) and nitrendipine plasma concentration was observed. Protein binding varied between 96.6 and 98.9%.