Pharmacokinetics of Nilvadipine in Healthy Volunteers

The pharmacokinetics of nilvadipine, a new antihypertensive and antianginal drug, were examined in healthy male volunteers. In a Latin square, three-way crossover design with a one-day run-in period, six subjects in three groups of two each were given single 2-, 4-, or 6-mg oral doses of nilvadipine after overnight fasting. Nilvadipine plasma concentrations up to 32 hours after drug treatment were determined by capillary column gas chromatography-negative-ion chemical ionization mass spectrometry (detection limit, 0.01 ng/mL). Nilvadipine urinary concentrations were determined by capillary column gas chromatography with electron capture detector (detection limit, 0.5 ng/mL). Nilvadipine plasma concentrations declined in a bi- or triexponential pattern after reaching the maximum plasma concentrations. The mean +/- standard deviation maximum plasma concentrations of 1.48 +/- 0.47, 3.48 +/- 0.53, and 6.69 +/- 1.54 ng/mL were attained from 1.08 to 1.50 hours after doses of 2, 4, and 6 mg, respectively. The elimination half-life was dose-independent and averaged 11.0 +/- 2.3 hours. The area under the plasma concentration-time curve increased in proportion to the dose. Nilvadipine was not detected in the urine. The pharmacokinetics of nilvadipine were generally linear over the dosage range studied. Besides the above model-independent pharmacokinetic parameters, model-dependent parameters were also obtained by curve-fitting the plasma data to a bi- or triexponential equation with zero-order absorption. Nilvadipine decreased blood pressure slightly and in a dose-dependent fashion.