Pharmacokinetics of Captopril and Its Effects on Blood Pressure During Acute and Chronic Administration and in Relation to Food Intake

Abstract

Nine patients with essential hypertension treated with bendroflumethiazide were given captopril 25 mg orally on three occasions to study the pharmacokinetics and blood pressure effects. Study 1: acute and fasting; study 2 and 3: with and without concomitant food intake (randomized order) after chronic treatment with captopril 25 mg three times a day for 4-5 weeks. Total and non-protein-bound captopril were measured by high performance liquid chromatography. Baseline mean arterial pressure (MAP) was lower during chronic treatment. MAP reduction was slightly more pronounced initially with concomitant food intake but thereafter the reductions were similar for up to 12 h in the three studies. Mean values for maximal MAP reductions and peak plasma concentrations of captopril occurred at the same time, but individual values were not correlated with each other. Peak plasma concentrations and area under the curve (AUC) of total and non-protein-bound captopril were slightly reduced with concomitant food intake. Chronic treatment did not consistently change the kinetics except for a slight prolongation of terminal half-life of non-protein-bound captopril. The AUC was higher during the chronic studies, probably owing to the baseline presence of captopril in plasma. It appears that captopril can be given twice daily and together with food without loss of blood pressure control in essential hypertension.