Kaye C M, Kumana C R, Leighton M, Hamer J, Turner P
Clin Pharmacol Ther. 1976 Apr;19(4):416-20. doi: 10.1002/cpt1976194416.
Using a balance, randomized, crossover design, single intravenous (1 mg/kg) or oral (3 X 100 mg) doses of acebutolol were administered at weekly intervals to 6 healthy volunteers. For each subject venous blood samples and timed urine collections were obtained after each treatment. Plasma and urinary acebutolol levels were measured by a spectrophotometric method that measures acebutolol and its N-acetyl metabolite (which has equivalent cardiac activity). Using a computer program, various pharmacokinetic parameters were estimated from the date of each subject. From the intravenous data (obtained up to 6 hr after dosing), the following mean (+/-SD) values were found: distribution half-life (T 1/2D), 0.60 (+/-0.43) hr, plasma elimination half-life (T 1/2El), 3.2 (+/-1.1) hr, apparent volume of distribution (VD), 224 (+/-69) L, and apparent VD/kg, 3.0 (+/-0.8) L/kg. Using the oral data (obtained up to 10 hr after dosing), the value for T 1/2El was 3.2 (+/-0.9) hr. The mean cumulative urinary recovery (expressed as % dose) after the intravenous route was about 60%, while that after the oral route was of the order of 35%, suggesting that about half of the oral dose reached the systemic circulation. The mean creatinine clearance of the 6 subjects was 103 (+/-7) ml/min, while the value (obtained between 2 and 4 hr after intravenous dosing) for renal clearance of acebutolol as measured was 298 (+/-68) ml/min and the corresponding plasma clearance was 818 (+/-64) ml/min. These results support the occurrence of substantial nonrenal elimination and renal tubular secretion.
采用平衡、随机、交叉设计，每周给6名健康志愿者静脉注射（1毫克/千克）或口服（3×100毫克）单次剂量的醋丁洛尔。对每个受试者，每次治疗后采集静脉血样并定时收集尿液。采用分光光度法测定血浆和尿液中的醋丁洛尔水平，该方法可测定醋丁洛尔及其具有同等心脏活性的N-乙酰代谢物。使用计算机程序，根据每个受试者的数据估算各种药代动力学参数。从静脉注射数据（给药后6小时内获得）中，得到以下平均（±标准差）值：分布半衰期（T 1/2D）为0.60（±0.43）小时，血浆消除半衰期（T 1/2El）为3.2（±1.1）小时，表观分布容积（VD）为224（±69）升，表观VD/千克为3.0（±0.8）升/千克。根据口服数据（给药后10小时内获得），T 1/2El的值为3.2（±0.9）小时。静脉给药后平均累积尿回收率（以剂量百分比表示）约为60%，而口服给药后约为35%，这表明口服剂量约有一半进入体循环。6名受试者的平均肌酐清除率为103（±7）毫升/分钟，静脉给药后2至4小时测得的醋丁洛尔肾清除率值为298（±68）毫升/分钟，相应的血浆清除率为818（±64）毫升/分钟。这些结果支持存在大量非肾消除和肾小管分泌。
