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.