Dose-dependent effects of felodipine on diuresis and natriuresis in healthy subjects

Abstract

We compared the effects of various acute doses of felodipine and placebo on diuresis and natriuresis in healthy men. The subjects were given felodipine, 1 and 3 mg as an intravenous infusion, and 5, 15, and 40 mg as an oral solution on 5 separate days. On each day blood pressure and heart rate were recorded and urine was collected for analysis of volume and sodium for 24 h. Felodipine induced a dose-dependent increase in heart rate and a dose-dependent decrease in diastolic blood pressure. These effects were maximal within 30 min of drug administration. Felodipine induced a maximal increase in diuresis of about 150% compared with placebo and a maximal increase in natriuresis of about 240%. The renal effects were most pronounced during the first 4 h after dose intake. During the 8-24 h interval, diuresis and natriuresis were lower than after placebo, but when the whole 24-h period was considered, no significant differences were found between felodipine and placebo in regard to sodium and water excretion. The most pronounced effects on diuresis and natriuresis were seen after moderate doses (3 mg i.v. and 15 mg orally). The response to the highest dose (40 mg orally) was somewhat less probably due to the excessive drop in diastolic blood pressure.