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Binding to serum α 1 ‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation
Author(s) -
Belpaire F.M.,
Bogaert M.G.,
Mugabo P.,
Rosseel M.T.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10253.x
Subject(s) - propranolol , atenolol , inflammation , metoprolol , pharmacology , pharmacokinetics , chemistry , medicine , endocrinology , blood pressure
1 The β‐blocking effect of 4 β‐adrenoceptor antagonists with different pharmacokinetic properties was studied after intravenous and intraportal administration to control rats and to rats with experimental inflammation. 2 In rats with inflammation the effects of propranolol and oxprenolol, which are mainly bound to α‐acid glycoprotein (α 1 ‐AGP), were significantly less after intravenous administration, but not after intraportal administration. In contrast, for metoprolol and atenolol, which are only negligibly serum bound, no difference was observed between control rats and rats with inflammation for either route of administration. 3 Total and unbound serum concentrations of propranolol were measured 20 min after intravenous and intraportal administration. 4 After intravenous administration, in the rats with inflammation total concentrations of propranolol were more than twice, and unbound concentrations less than half those of control rats. After intraportal administration the total concentrations were 8 times, and the unbound concentrations 3 times higher in the rats with inflammation. 5 There was a significant correlation between the β‐blocking effect and the unbound concentrations of propranolol after intravenous administration, but not after intraportal administration. The latter finding is probably because the unbound concentrations were supramaximal.