Pharmacokinetics and hemodynamic effects of long-term nisoldipine treatment in hypertensive patients.

In six patients with essential hypertension, the pharmacokinetics of nisoldipine were investigated before, during, and after 4 weeks of treatment. On day 1, nisoldipine was infused intravenously (i.v. 2 mg in 2 h); on day 2, oral nisoldipine treatment (10-mg tablets twice daily) was started for 4 weeks. During this period, patients came to the hospital six times, on which occasions blood samples were taken for the determination of trough and peak concentrations of nisoldipine. After 4-week treatment, the infusion experiment was repeated. In the first infusion experiment, systemic clearance was 1.02 +/- 0.23 L/min (mean +/- SD), terminal half-life (t1/2) was 15.4 +/- 6.7 h, and volume of distribution was 5.9 +/- 1.8 L/kg. After 4 weeks, these parameters had not changed significantly. Nisoldipine lowered blood pressure (BP) in all patients, whereas forearm blood flow and heart rate (HR) increased. Neither were the hemodynamic changes different after the oral treatment period, although basal BP was lower than before oral treatment. No accumulation of nisoldipine occurred during the 4-weeks treatment period.