Polymorphic acetylation of procainamide in man
Polymorphic acetylation of procainamide in man
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人体内普鲁卡因酰胺的多态性乙酰化
DOI：
10.1002/cpt1975176722
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发表时间：
1975
影响因子：
6.7
通讯作者：
H. Warner
中科院分区：
文献类型：
--
作者：
M. Reidenberg;D. Drayer;M. Levy;H. Warner
在已知乙酰化表型（氨苯砜表型）服用普鲁卡因胺超过3天的人群中，通过薄层色谱（TLC）密度测定法测定N-乙酰普鲁卡因胺（NAPA）和普鲁卡因胺血浆和尿液浓度。最后一次给药后3小时，快速乙酰化者的血浆NAPA /普鲁卡因胺比率（平均值± SD）为1.8 ± 0.59（N = 8），慢速乙酰化者为0.61 ± 0.09（N = 6）（p < 0.001）。NAPA的肾清除率平均为同时测量的内生肌酐清除率的1.2倍，而普鲁卡因胺清除率约为肌酐清除率的两倍。慢乙酰化剂和快乙酰化剂在药物的肾脏清除率或尿液pH值方面无差异，表明这两组之间血浆NAPA /普鲁卡因胺比值的差异是由于其乙酰化速率的差异。因此，普鲁卡因胺很可能在人体内被多态性N-乙酰转移酶乙酰化。反映血液水平差异的是，尿液中的NAPA/普鲁卡因胺比值（末次给药后90 - 180分钟采集）在快速乙酰化者中高于缓慢乙酰化者。NAPA和普鲁卡因胺的血浆蛋白结合相似。由于NAPA似乎具有类似于普鲁卡因胺的抗惊厥效力，NAP A可能有助于普鲁卡因胺治疗的抗惊厥活性，特别是在遗传快速乙酰化中。
N‐Acetylprocainamide (NAPA) and procainamide plasma and urine concentrations were determined by thin‐layer chromatography (TLC) densitometry in people of known acetylator phenotype (dapsone phenotyping) taking procainamide for more than 3 days. The plasma NAPA / procainamide ratio 3 hr after the last dose for fast acetylators (mean ± SD) is 1.8 ± 0.59 (N = 8) and for slow acetylators, 0.61 ± 0.09 (N = 6)(p < 0.001). The renal clearance of NAPA averaged 1.2 times the simultaneously measured endogenous creatinine clearance, whereas procainamide clearance was approximately double the creatinine clearance. There was no difference between slow and rapid acetylators in the renal clearance of either drug or the urine pH, indicating that the difference in plasma NAPA /procainamide ratios between these two groups is due to differences in their rates of acetylation. Therefore, procainamide is probably acetylated by the polymorphic N‐acetyltransferase in man. Reflecting the blood level differences, the NAPA/procainamide ratio in urine (collected 90 to 180 min after last dose) was found to be higher in rapid than in slow acetylators. The plasma protein binding of NAPA and of procainamide are similar. Since NAPA seems to have an antiarrhythmic potency similar to procainamide, NAP A probably contributes to the antiarrhythmic activity of procainamide therapy, especially in genetic rapid acetylators.