Atkinson A J, Ruo T I, Piergies A A, Breiter H C, Connelly T J, Sedek G S, Juan D, Hubler G L, Hsieh A M
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Clin Pharmacol Ther. 1989 Aug;46(2):182-9. doi: 10.1038/clpt.1989.124.
N-Acetylprocainamide (NAPA) absorption and disposition were profiled in five patients with ventricular arrhythmias by the simultaneous intravenous administration of NAPA-13C and oral administration of a 500 mg NAPA hydrochloride tablet. NAPA distribution was modeled with a three compartment mammillary system. The central compartment volume of 14.1 +/- 2.6 L (mean +/- SD) was similar to expected intravascular space, corrected for NAPA partitioning between erythrocytes and plasma. Other compartment volumes, intercompartmental and nonrenal clearances, and the steady-state distribution volume of 1.45 +/- 0.09 L/kg were similar to normal subject values. The least-squares estimate of 1.67 for the NAPA renal clearance/creatinine clearance ratio was similar to the value of 1.68 previously reported for functionally anephric patients and showed the expected age-associated decrease. The oral NAPA dose was 78.0% +/- 11.7% absorbed and interindividual variation in NAPA absorption was correlated with fast intercompartmental clearance (r = 0.89, p = 0.045). Because fast intercompartmental clearance partly reflects splanchnic blood flow, hemodynamic changes may affect NAPA bioavailability, as has been found for procainamide.
通过同时静脉注射N-乙酰普鲁卡因胺（NAPA）-13C和口服500毫克盐酸NAPA片，对5例室性心律失常患者的NAPA吸收和处置情况进行了分析。NAPA分布采用三室乳头系统建模。中央室容积为14.1±2.6升（平均值±标准差），与预期的血管内空间相似，已根据NAPA在红细胞和血浆之间的分配进行校正。其他室容积、室间和非肾清除率以及稳态分布容积为1.45±0.09升/千克，与正常受试者的值相似。NAPA肾清除率与肌酐清除率之比的最小二乘估计值为1.67，与先前报道的功能性无肾患者的1.68值相似，并显示出预期的与年龄相关的下降。口服NAPA剂量的吸收率为78.0%±11.7%，NAPA吸收的个体间差异与快速的室间清除率相关（r = 0.89，p = 0.045）。由于快速的室间清除率部分反映了内脏血流量，血流动力学变化可能会影响NAPA的生物利用度，正如普鲁卡因胺的情况一样。
