The effect of six beta-adrenolytics and labetalol on hepatic biotransformation studied by antipyrine test, in man.
The study was aimed at a comparison of the effects of various beta-blockers (propranolol, pindolol, nadolol, atenolol, metoprolol, acebutolol, labetalol) on hepatic biotransformation within the short- and long-term treatment. The study was undertaken in 125 patients with arterial hypertension and/or coronary heart disease. The rate of hepatic metabolism was estimated by antipyrine test. After several months' administration of "pure" beta-adrenolytics the antipyrine half-time increased (means + SD) from 16.6 +/- 4.4 to 22.1 +/- 8.0 h (p less than 0.01), whereas antipyrine clearance decreased from 27.4 +/- 11.5 to 21.9 +/- 8.7 ml X min-1 (p less than 0.01). Deterioration of antipyrine elimination following beta-adrenolytics administration occurred independently of such properties as cardioselectiveness, intrinsic sympathomimetic activity, membrane stabilizing activity and the liver first-pass effect. After three months' labetalol (alpha + beta-blocker) administration, the antipyrine half-time decreased from the average 18.5 +/- 5.1 to 15.0 +/- 4.4 h (p less than 0.05), whereas its clearance increased from 30.3 +/- 2.7 to 36.3 +/- 10.8 min-1 (p less than 0.05). The results indicate that labetalol accelerates the rate of hepatic biotransformation as opposed to "pure" beta-adrenolytics, deteriorating the hepatic metabolism efficiency.
Adamska-Dyniewska
H
H
Dziekański
S
S
Pruszczyński
J
J
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000328:Adult; D000983:Antipyrine / Q000097:blood; D001711:Biotransformation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007700:Kinetics; D007741:Labetalol / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged
D000319:Adrenergic beta-Antagonists; D007741:Labetalol; D000983:Antipyrine