Branch R A, Herman R J
Br J Clin Pharmacol. 1984;17 Suppl 1(Suppl 1):77S-84S. doi: 10.1111/j.1365-2125.1984.tb02432.x.
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.
所有需要在消除前进行代谢的β-肾上腺素能受体阻滞剂，由于酶诱导作用，都可能存在药物相互作用。然而，关于这方面的数据仅在人体中针对普萘洛尔、美托洛尔和阿普洛尔有报道。横断面人群研究表明，环境因素，如年轻人吸烟，能够影响普萘洛尔的口服清除率。比较服用利福平及戊巴比妥前后美托洛尔、阿普洛尔和普萘洛尔个体内清除率的长期研究表明，口服清除率提高了50% - 500%。诱导剂除了影响药物代谢能力外，还能影响内在清除率、肝血流量和蛋白结合，这表明药代动力学处置的变化可能很复杂。酶诱导呈现剂量和时间依赖性关系。受试者之间酶诱导的最大程度相似。诱导前后药物代谢的个体间变异范围相似。酶诱导后β-肾上腺素能受体稳态药物浓度的降低幅度足够大，如果不调整剂量，预期会出现药效学反应改变。
