Kinetics of medroxalol, a β- and α-adrenoceptor antagonist

Abstract

Medroxalol is a new antihypertensive with both .beta.- and .alpha.-adrenergic blocking properties. Eight healthy men received single oral doses of 400, 800 and 1200 mg medroxalol and a single i.v. dose of 1 mg/kg body wt on 4 occasions separated by at least 2 wk. Plasma medroxalol concentrations were assayed up to 24 h after each dose by a specific high-pressure liquid chromatographic assay. Urinary excretion of the parent compound was also determined. Following oral doses, medroxalol reached peak plasma concentrations within 2.5-3 h. The t1/2 [half-life] of the terminal decay phase was 11.1 h. Mean apparent volume of distribution (aVD) was 11.2-16.4 l/kg, and mean total body clearance (ClT) was 0.73-0.99 l/h per kg. Mean urinary recovery of parent drug within 48 h was 2.3, 3.9 and 3.6% after the oral doses compared to 8.2% after the i.v. dose. Bioavailability estimated from AUC was 27.2% after 400 mg, 31.3% after 800 mg and 37.4% after 1200 mg by mouth. Since aVD, t1/2, ClT and urinary excretion did not differ significantly after the 3 oral doses, medroxalol kinetics appear to follow a dose-linear model.