The effect of hydralazine on the pharmacokinetics of metoprolol, nadolol, and acebutolol has been studied by measuring drug concentrations in plasma, serum, and urine. Metoprolol is affected by hydralazine, the AUC and Cmax being significantly increased. The kinetics of acebutolol and its major metabolite, diacetolol, are unaffected. Poor absorption of the polar beta blocker, nadolol, does not allow a firm conclusion to be drawn regarding the effect of hydralazine. It is concluded that only beta blockers with a substantial first-pass loss are likely to be significantly affected by hydralazine.
Plasma concentrations of metoprolol, propranolol oxprenolol, acebutolol and its metabolite diacetolol were measured after single oral doses in young health volunteers. In order to assessed the inter- and intra-subject variability the following pharmacokinetic parameters were compared: AUC0(24), Cmax, tmax and t 1/2. The smallest variation in inter-subject variability was seen with oxprenolol and acebutolol: intrasubject variability was more uniform. Female volunteers taking an oral contraceptive generally had higher AUC0(24) and Cmax values than those not. This finding reached statistical significance only for metoprolol AUC0(24).
1 The effect of acebutolol, a relatively selective -adrenoceptor blocking drug and propranolol, a non-selective one, on the hypoglycaemic action of glibenclamide after an oral glucose load has been investigated in a group of maturity-onset diabetic patients. 2 Glibenclamide significantly reduced the blood glucose levels and both acebutolol and propranolol, at therapeutic doses, were found to modify this action significantly. 3 The effect of acebutolol was slightly less than that of propranolol. The difference was not statistically significant. 4 The modes of action of sulphonylureas are reviewed and it is suggested that /8-adrenoceptor blockers may modify their effect on insulin release. This appears to be a drug interaction rather than an effect of ,(-adrenoceptor blockade on glucose tolerance.
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