Observations on the clinical pharmacology and plasma concentrations of diacetolol, the major human metabolite of acebutolol.

1 The pharmacological effects and plasma levels of diacetolol, the major human metabolite of acebutolol, were measured in a double-blind, balanced study in which five healthy men received single oral doses of diacetolol 100, 200, 400 and 800 mg, or placebo, at weekly intervals. 2 Resting and exercise heart rate (HR), forced expiratory volume in 1 second (FEV1), resting and exercise peak expiratory flow rate (PEFR), and plasma concentrations of diacetolol were determined at 0, 2, 4, 6, 8 and 24 h after each treatment. 3 Diacetolol caused a slight dose-related reduction in resting HR and a substantial dose-related reduction in exercise HR. AT the same time it was found that diacetolol had no significant effects on FEV1 and resting and exercise PEFR. 4 Mean highest observed plasma concentrations (ng/ml) of diacetolol were 177 at a mean of 4.4 h after the 100 mg dose, 243 at 4.0 h after the 200 mg dose, 807 at 5.2 h after the 400 mg dose, and 1,306 at 4.4 h after the 800 mg dose. 5 Using the mean data, there was a strong correlation (r = 0.90) between % reduction in exercise HR and the logarithm of the plasma concentration of diacetolol. 6 Diacetolol exhibits marked cardiac beta-adrenoceptor blocking activity in man which is still evident 24 h after the administration of the higher doses of the drug. No adverse effects on pulmonary function could be detected.