ABSTRACT
Biotransformation in the liver was tested with antipyrine elimination test in 41 patients treated with prazosin for 3 months (Minipress Pfizer, 1-4 mg a day) or prazosin combined with beta-adrenolytic agents (propranolol 40-80 mg; metoprolol 100-200 mg daily). It was found that T0.5 of antipyrine is shortened in patients treated with prazosin alone by 3 h/p greater than .05/while in the patients treated with prazosin whom previously--adrenalytics were given by 7.5 h/p greater than 0.01/. Antipyrine half-life during the treatment with beta-adrenolytics was prolonged by + 5.3 h/p greater than .05/while during the combined therapy with these agents and prazosin - 3.8 h. These results indicate that prazosin contrary to beta-adrenolytics, does not affect biotransformation in the liver. During combined therapy with prazosin and beta-adrenolytics, unfavourable effect of the latter in prevailing. Replacement of beta-adrenolytics with prazosin may prevent unfavourable effect of the former on liver functioning and may increase the safety of the hypotensive treatment.
Subject(s)
Antipyrine/pharmacokinetics , Hypertension/drug therapy , Liver/metabolism , Metoprolol/therapeutic use , Prazosin/therapeutic use , Propranolol/therapeutic use , Adult , Aged , Biotransformation/drug effects , Humans , Hypertension/metabolism , Liver/drug effects , Metoprolol/toxicity , Middle Aged , Propranolol/toxicityABSTRACT
18 patients aged 40-50 with diagnosed hypertension (II class by WHO) underwent the study. SOD-1 activity, platelets MDA concentration and degree of platelets aggregation were estimated before and after 1.5 and 24 hours of administration of 12.5 mg captopril single dose. Values of evaluated parameters significantly changed after 1.5 hours of captopril administration: SOD-1 activity increased whereas MDA concentration and platelets aggregation decreased; after 24 hours of drug administration values returned to initial ones. It suggests inhibitory effect of captopril on lipids peroxidation and platelets reactivity.
Subject(s)
Captopril/therapeutic use , Hypertension/drug therapy , Malonates/blood , Malondialdehyde/blood , Superoxide Dismutase/blood , Adult , Blood Platelets/drug effects , Blood Platelets/metabolism , Enzyme Activation/drug effects , Humans , Hypertension/blood , Malondialdehyde/antagonists & inhibitors , Middle AgedABSTRACT
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.
