Miners J O, Wing L M, Lillywhite K J, Smith K J
Br J Clin Pharmacol. 1984 Dec;18(6):853-60. doi: 10.1111/j.1365-2125.1984.tb02555.x.
The effects of separate 1 week pre-treatments with each of the beta-adrenoceptor antagonists, propranolol (80 mg every 12 h), metoprolol (100 mg every 12 h) and atenolol (50 mg once daily), on the disposition of a single i.v. dose of tolbutamide were studied in six healthy volunteers. In addition, the effects of a 1 week pre-treatment with metoprolol (100 mg every 12 h) and atenolol (50 mg once daily) on the disposition of orally and i.v. administered lignocaine were determined in seven healthy subjects. Tolbutamide clearance, half-life, volume of distribution and plasma protein binding were not altered by the beta-adrenoceptor blocker pre-treatments. Similarly, neither metoprolol nor atenolol had a significant effect on the systemic clearance, apparent oral clearance or other dispositional parameters of lignocaine. 'Therapeutic' plasma concentrations of the beta-adrenoceptor blockers were confirmed on each study day. It is concluded that the inhibition of oxidative drug metabolism previously reported for lipophilic beta-adrenoceptor blockers may be selective for different forms of cytochrome P450 and possible concentration-dependent.
在六名健康志愿者中研究了分别用β-肾上腺素受体拮抗剂普萘洛尔（每12小时80毫克）、美托洛尔（每12小时100毫克）和阿替洛尔（每日一次50毫克）进行1周预处理对单次静脉注射甲苯磺丁脲处置的影响。此外，在七名健康受试者中确定了用美托洛尔（每12小时100毫克）和阿替洛尔（每日一次50毫克）进行1周预处理对口服和静脉注射利多卡因处置的影响。β-肾上腺素受体阻滞剂预处理未改变甲苯磺丁脲的清除率、半衰期、分布容积和血浆蛋白结合率。同样，美托洛尔和阿替洛尔对利多卡因的全身清除率、表观口服清除率或其他处置参数均无显著影响。在每个研究日均证实了β-肾上腺素受体阻滞剂的“治疗性”血浆浓度。得出的结论是，先前报道的亲脂性β-肾上腺素受体阻滞剂对氧化药物代谢的抑制作用可能对细胞色素P450的不同形式具有选择性，并且可能是浓度依赖性的。
