Comparison of beta-adrenoceptor antagonists as modulators of drug metabolism: effect of lipophilicity on microsomal phase I and II reactions.
The effect of beta-adrenoceptor antagonists with varying lipophilicity on microsomal phase I and II reactions was investigated using rat hepatic microsomes. The degree of inhibition of ethoxyresorufin deethylase paralleled octanol/water partition coefficients: propranolol greater than alprenolol greater than timolol greater than metoprolol greater than atenolol. Propranolol (highly lipophilic) and atenolol (hydrophilic) also had widely different effects on 7-ethoxycoumarin deethylase inhibition and on disopyramide N-dealkylation. However the inhibition of harmol conjugation was not related in the same way to octanol/water partition coefficient as was the phase I reactions.
D015660:7-Alkoxycoumarin O-Dealkylase; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019363:Cytochrome P-450 CYP1A1; D004206:Disopyramide / Q000378:metabolism; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010105:Oxygenases / Q000037:antagonists & inhibitors; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012995:Solubility
D000319:Adrenergic beta-Antagonists; D004364:Pharmaceutical Preparations; D001262:Atenolol; D011433:Propranolol; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1; D004206:Disopyramide