PHARMACOKINETICS AND PHARMACODYNAMICS OF TWO NEW ~-BLOCKERS

Metipranolol from Czechoslovakia Metipranolol, used as Trimepranol' (Spofa) in Czechoslovakia. was recently introduced by Boehringer Mannheim as 'Disorat' and also in combination with butizid as ~Torrat'. Its pharmacokinetics were studied after a single 40mg 'oral dose or repeated 20mg doses (bid for 8 days) in 39 healthy volunteers. After a single dose the mean absorption half-life was less than 20 min and the elimination half-life was 4 hours. With chronic dosing the half-life was 2.5 hours. Antagonism of isoproterenol (isoprenaline)­induced and exercise tachycardia showed a clear ~-blocking effect after single and repeated doses. The plasma level and ~-blocking effect did not decline in parallel; although the drug disappeared from plasma much earlier, the response to both types of ~-stimuli was still reduced 8-10 hours after a dose of metipranolol. Twice-daily dosage is therefore recommended, starting with 20-30mg/ day and gradually increasing the dose to obtain an optimum effect. Mayer, O. et al.: International Journal of Clinical Pharmacology, Therapy and Toxicology 18: 113 (Mar 1980)

And mepindolol sulphate from Germany Mepindolol sulphate (Schering AG, Berlin) is a new non-selecctive ~-blocker with a slight sympathomimetic intrinsic activity. Five healthy male volunteers were given ~ IY dose of 1.19mg of 2-methyl-14C-mepindolol sulphate and a 20mg oral dose a week later. The half-life of unchanged drug in plasma was 4.1 hours and of total l4C activity (drug +. metabolites), 6.0 hours. The bioavailability after an oral dose was 82 ± II %, and the maximum plasma level (37 .2ng/ mn was reached after 1.6 hours. In 3 subjects given 2.5mg bid for 8 days, the effect on heart rate was almost constant as soon as the second day. On average, 65 % of the maximum:effect was still present 1-2 hours after the last dOse.· EX<;ept on day 2; there was no accumulation of the drug or its metabolites during the study. Bonelli, J. et aI.: International Journal of Clinical Pharmacology, Therapy and Toxicology 18: 169 (Apr 1980)

0156-2703/80/0614-0015 $00.50/0 CADIS Press INPHARMA 14Jun 1980 15