Pharmacokinetics of adimolol after single and multiple dose administration in healthy volunteers

The pharmacokinetic properties of adimolol (MEN 935), a new antihypertensive agents with predominantly beta-receptor blocking and additional alpha-adrenolytic activity were investigated in healthy volunteers. Study A subjects (n = 6) received single intravenous doses of 5 mg adimolol and single oral doses of 200 mg capsules, 200 mg tablets and 100 mg tablets on four occasions separated by at least two weeks. Study B subjects (n = 6) were given single intravenous doses of 5 mg and single oral doses of 100 mg of the 14C-labelled drug on two different occasions. Study C subjects (n = 6) were administered multiple oral doses of 100 mg adimolol daily for five days, and three weeks later 50 mg daily for five days. Adimolol plasma concentrations were assayed over seven days following each single dose using a specific and sensitive high-pressure liquid chromatographic method. The plasma concentration data obtained from the single i.v. dose studies were individually fitted to an open four-compartment model. To describe mathematically the single oral dose plasma level data, two compartments were added to the model to take care of the absorption. Irrespective of the route of administration, the doses and formulations given, all plasma concentration curves could be described with similar pharmacokinetic parameters. Plasma concentration curves predicted by the open four-compartment model were fully confirmed by the actual data obtained after chronic oral administration. The terminal half-life averaged 12 h following intravenous and 15 h after oral administration. The peak plasma concentration was reached on average 4 h following oral administration.(ABSTRACT TRUNCATED AT 250 WORDS)