Schneck D W, Grove K, Dewitt F O, Shiroff R A, Hayes A H
J Pharmacol Exp Ther. 1978 Jan;204(1):219-25.
The objectives of this study were to investigate: 1) the rat acetylator phenotype, 2) the systemic availability of oral procainamide (PA), 3) the kinetic disposition of PA and its N-acetyl metabolite (NAPA) and 4) the relationship between PA dose and steady-state blood PA and NAPA levels. The rat acetylator phenotype seems to be monomorphic in type. The systemic availability of PA was estimated to be 78%. The half-life (T 1/2) of PA elimination was 55 minutes and that of NAPA was 51 minutes. PA clearance was 64 ml/kg/min and NAPA clearance 22.4 ml/kg/min. The apparent distribution volume for PA was 4.92 liters/kg and for NAPA 1.64 liters/kg. Acetylation accounted for 38% of PA disposition, urinary excretion 34% and other metabolism 28%. Urinary excretion of NAPA accounted for 72% of administered drug. Steady-state blood PA levels showed a linear increase with dose whereas NAPA did not. The latter observation suggests saturation of PA acetylation at higher PA doses.
1）大鼠乙酰化表型；2）口服普鲁卡因胺（PA）的全身可用性；3）PA及其N-乙酰代谢物（NAPA）的动力学处置；4）PA剂量与稳态血药PA和NAPA水平之间的关系。大鼠乙酰化表型似乎为单一型。PA的全身可用性估计为78%。PA消除的半衰期（T 1/2）为55分钟，NAPA的半衰期为51分钟。PA清除率为64 ml/kg/min，NAPA清除率为22.4 ml/kg/min。PA的表观分布容积为4.92升/千克，NAPA的表观分布容积为1.64升/千克。乙酰化占PA处置的38%，尿排泄占34%，其他代谢占28%。NAPA的尿排泄占给药药物的72%。稳态血药PA水平随剂量呈线性增加，而NAPA并非如此。后一观察结果表明，在较高PA剂量下PA乙酰化饱和。
