Pharmacokinetics of bendroflumethiazide alone and in combination with propranolol and hydralazine

Bendroflumethiazide (Bft) was administered to 6 healthy subjects at 3 different dose levels (2.5, 5 and 10mg) in a cross-over design, either as capsules (2.5mg) or as tablets (5mg). Its pharmacokinetics were evaluated then and following administration of a fixed combination of Bft and propranolol and hydralazine to a further 7 volunteers. Plasma and urinary concentrations of Bft were determined by a new fluorimetric - thin-layer chromatography procedure. Peak plasma levels occurred after 2-3h and averaged 15, 27 and 45 microgram/l in the three dose groups. Areas under the plasma concentration - time curves (AUC0 leads to 12), which were 75, 147 and 250 microgram 1(-1)h respectively, and cumulative urinary recovery (20%) were independent of the dose administered and the type of formulation. Thus Bft kinetics proved to be linear within the dose range evaluated. The plasma clearance was calculated to be 505 ml/min, renal clearance 108 ml/min and nonrenal clearance 396 ml/min. Bioavailability of Bft was not altered following administration of the fixed combination. The amount of propranolol found in the circulation did not change, whereas that of hydralazine (determined as apparent hydralazine) increased by 59% when the fixed combination was administered.