Coyle J D, Boudoulas H, Lima J J
College of Pharmacy, Ohio State University, Columbus 43210.
Biopharm Drug Dispos. 1991 Nov;12(8):599-612. doi: 10.1002/bdd.2510120806.
The purpose of this study was to determine the pharmacokinetics of acecainide (formerly N-acetylprocainamide) in six normal subjects of known acetylator phenotype. Three subjects were fast acetylators and three slow acetylators by sulfapyridine phenotyping criteria. Each subject received a 20-min, 3 mg kg-1 intravenous acecainide infusion. Concentrations of acecainide, procainamide, and their deethylated metabolites were measured in serum and urine samples using HPLC. Acecainide renal clearance, nonrenal clearance, steady-state volume of distribution, and other pharmacokinetic parameters were estimated using standard approaches. Acecainide renal clearance and steady-state volume of distribution were (mean +/- SD) 13.6 +/- 1.581 h-1 and 135 +/- 20.31, respectively, and were not significantly different in fast and slow acetylators. Acecainide nonrenal clearance in the six subjects was 3.0 +/- 1.01 h-1; however, nonrenal clearance in slow acetylators was 1.8 times that in fast acetylators (3.9 vs 2.21 h-1, p = 0.012) with clear separation of the subjects into two groups when the data were grouped by acetylator phenotype. The nonrenal clearance of acecainide was inversely correlated with percentage sulfapyridine acetylation. Computer simulations were conducted to explore possible explanations for the observed difference in nonrenal clearance.
本研究的目的是确定醋卡尼（原N - 乙酰普鲁卡因胺）在六名已知乙酰化表型的正常受试者中的药代动力学。根据磺胺吡啶表型分析标准，三名受试者为快速乙酰化者，三名受试者为慢速乙酰化者。每名受试者接受了20分钟、3毫克/千克的醋卡尼静脉输注。使用高效液相色谱法测定血清和尿液样本中醋卡尼、普鲁卡因胺及其脱乙基代谢物的浓度。使用标准方法估算醋卡尼的肾清除率、非肾清除率、稳态分布容积和其他药代动力学参数。醋卡尼的肾清除率和稳态分布容积分别为（均值±标准差）13.6±1.581小时-1和135±20.31，快速乙酰化者和慢速乙酰化者之间无显著差异。六名受试者中醋卡尼的非肾清除率为3.0±1.01小时-1；然而，慢速乙酰化者的非肾清除率是快速乙酰化者的1.8倍（3.9对2.21小时-1，p = 0.012），当按乙酰化表型对数据进行分组时，受试者明显分为两组。醋卡尼的非肾清除率与磺胺吡啶乙酰化百分比呈负相关。进行了计算机模拟以探究观察到的非肾清除率差异的可能原因。
