Meffin P J, Winkle R A, Peters F A, Harrison D C
Clin Pharmacol Ther. 1977 Nov;22(5 Pt 1):557-67. doi: 10.1002/cpt1977225part1557.
The disposition of acebutolol has been studied following intravenous doses of 0.25 to 1.0 mg/kg in 9 healthy subjects using a specific chromatographic assay to determine concentrations of drug in blood. The mean blood clearance was 6.55 ml/min/kg and the mean renal clearance, 2.68 ml/min/kg. Blood clearance was found to have a coefficient of variation of 14% for the group, to be independent of dose, and to remain essentially constant over approximately 3 wk. The fraction of the dose excreted in the urine unchanged was 0.405. Data were fitted to an equation for a two-compartment model. The mean fast and slow half-lives were 6.08 and 156.8 min, respectively. The volume of the central compartment was 0.223 L/kg, and the volume of distribution at steady-state was 1.165 L/kg. The fraction of acebutolol unbound to plasma proteins was 0.743 and was independent of drug concentration in the range examined. Data obtained from 15-min infusions were used to predict plateau blood concentrations with good accuracy during an 8-hr dosage regimen.
在9名健康受试者中，静脉注射剂量为0.25至1.0mg/kg的醋丁洛尔后，采用特定的色谱分析法测定血液中的药物浓度，对醋丁洛尔的处置情况进行了研究。平均血液清除率为6.55ml/（min·kg），平均肾脏清除率为2.68ml/（min·kg）。发现该组的血液清除率变异系数为14%，与剂量无关，并且在大约3周内基本保持恒定。以原形经尿液排泄的剂量分数为0.405。数据拟合为二室模型方程。平均快半衰期和慢半衰期分别为6.08分钟和156.8分钟。中央室容积为0.223L/kg，稳态分布容积为1.165L/kg。未与血浆蛋白结合的醋丁洛尔分数为0.743，在所研究的浓度范围内与药物浓度无关。在8小时给药方案期间，利用15分钟输注获得的数据能够准确预测稳态血药浓度。
