Pharmacokinetics and haemodynamic effects of felodipine as monotherapy in hypertensive patients

Abstract

The acute and steady-state pharmacokinetics and dynamics of felodipine as monotherapy have been studied in 12 hypertensive patients. Felodipine was acutely administered by a constant infusion, 1.5 mg over a 30-min period, or as a 10-mg tablet. Chronic administration was performed on a fixed dose of 10 mg b.i.d. for 28 days. The systemic availability of felodipine after the acute dose was 15%, and at steady state 12% (N.S.), with a 3-fold variation between patients. The mean plasma clearance was 0.6 L/h. The half-life measured in the 4- to 10-h interval after dose was about the same: 3.4, 3.2, and 3.3 h after the i.v. dose, the acute oral dose, and at steady state, respectively. The mean terminal half-life was 24.5 h after the oral dose at steady state. Both the intravenous and the oral doses of felodipine decreased the diastolic blood pressure for about 8 hours after dosing. The reduction in diastolic blood pressure was about 20 mmHg 1 to 2 hours after dose. Supine diastolic blood pressure was significantly reduced up to 48 h after dose at steady state. Maximum reduction of diastolic blood pressure (-22 mmHg) already occurred on the first day of treatment, while systolic blood pressure was further decreased during chronic treatment. There was a correlation between the individual maximum decrease in diastolic blood pressure after the acute oral dose with that after repeated administration (r2 = 0.70, p less than 0.01). Changes in heart rate were non-significant at steady state.