Mallein R, François B, Rondelet J, Ksavrelof H
Eur J Drug Metab Pharmacokinet. 1984 Apr-Jun;9(2):141-8. doi: 10.1007/BF03189617.
The pharmacokinetics of Pyridinol carbamate (PDC) were studied over a 48 hour period in 14 patients with Chronic Renal Failure (C.R.F.) and in 10 normal controls. Following a single oral dose of 1 gm of PDC, the serum was assayed for PDC and M1 (monodemethylated PDC, the 1st metabolite) and the urine for PDC: M1, and M2 (second metabolite). The C max of PDC was found to be increased in the patients with C.R.F. when compared with the controls (21.8 +/- 5.26 micrograms VS 18.28 +/- 4.58 micrograms) but the half-life was unchanged (6.56 +/- 3.93 h VS 5.86 +/- 1.5 h). There was no difference between the C max of M1 of the patients and that of the controls (7.04 +/- 1.5 micrograms VS 6.49 +/- 0.84 micrograms), but there was an increase in the half-life (21.28 +/- 15.86 h VS 11.78 +/- 5.86) and of the area under curve (319.8 +/- 170.8 micrograms VS 182.6 +/- 78.5 micrograms ml-1 h). The overall excretion of PDC, M2 and particularly of M1 was found to be decreased and a higher concentration of PDC was noted in the urine of C.R.F. group. A correlation between the concentration of M2 and the severity of C.R.F. was observed, in that lower concentration or the absence of M2 in the 1st 6 hour urine sample appeared to be directly related to the severity of renal failure. Current evidence suggests that the N-demethylation of PDC remains normal in CRF and that there is enhanced transformation of M1 to ;M2.
在14名慢性肾衰竭（CRF）患者和10名正常对照者中，对吡啶醇氨基甲酸酯（PDC）的药代动力学进行了48小时的研究。单次口服1克PDC后，检测血清中的PDC和M1（单去甲基化PDC，第一种代谢物）以及尿液中的PDC、M1和M2（第二种代谢物）。发现CRF患者中PDC的Cmax与对照组相比有所增加（21.8±5.26微克对18.28±4.58微克），但半衰期未改变（6.56±3.93小时对5.86±1.5小时）。患者和对照组M1的Cmax之间没有差异（7.04±1.5微克对6.49±0.84微克），但半衰期有所增加（21.28±15.86小时对11.78±5.86小时），曲线下面积也有所增加（319.8±170.8微克对182.6±78.5微克·ml⁻¹·h）。发现PDC、M2尤其是M1的总体排泄减少，且CRF组尿液中PDC的浓度更高。观察到M2浓度与CRF严重程度之间存在相关性，即最初6小时尿液样本中M2浓度较低或不存在似乎与肾衰竭严重程度直接相关。目前的证据表明，CRF中PDC的N-去甲基化保持正常，且M1向M2的转化增强。
