title: Enzyme induction and beta-adrenergic receptor blocking drugs.
abstract: All beta-adrenergic receptor blockers that require metabolism prior to elimination are potentially subject to drug interactions due to enzyme induction. However, data is only available in man for propranolol, metoprolol and alprenolol. Cross-sectional population studies suggest that environmental factors, such as smoking in the young, are able to influence the oral clearance of propranolol. Long-term studies comparing within-subject clearances of metoprolol, alprenolol and propranolol before and after rifampicin and pentobarbitone, indicate that oral clearance is increased by 50%-500%. Inducing agents can influence intrinsic clearance, liver blood flow, and protein binding in addition to drug metabolising ability, indicating that changes in pharmacokinetic disposition may be complex. Enzyme induction exhibits both dose and time dependency relationships. The maximal extent of enzyme induction is similar between subjects. The range of intersubject variation in drug metabolism is similar before and after induction. The reduction in steady-state beta-adrenergic receptor drug concentration following enzyme induction is sufficiently large that an altered pharmacodynamic response would be expected if no dosage modification is made.
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000983:Antipyrine / Q000378:metabolism; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D010634:Phenobarbital / Q000494:pharmacology; D011433:Propranolol / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D012907:Smoking
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D000983:Antipyrine; D012293:Rifampin; D010634:Phenobarbital