Mitchell D, Wagner C, Stone W J, Wilkinson G R, Schenker S
Gastroenterology. 1976 Dec;71(6):1043-9.
Pyridoxal 5'-phosphate (PLP), the coenzyme form of vitamin B6, is essential for many biochemical reactions in the body. Studies in experimental animals have suggested that the liver is a primary site for the formation of PLP circulating in the plasma, and that it may also participate in its degradation. This study evaluates, for the first time, the effects of liver disease in man on the regulation of plasma PLP. The plasma PLP level was measured before and sequentially after the rapid intravenous administration of 50 mg of pyridoxine to patients with alcoholic cirrhosis, acute hepatitis, and extrahepatic obstruction, and to normal control subjects. The base line plasma PLP concentration was significantly lower in cirrhotic patients than in normal persons (P less than 0.025), and there was a tendency for it to be reduced in patients with extrahepatic obstruction. After administration of pyridoxine there was a significant increase in the plasma PLP level over a 2- to 12-hr period, after which the concentration returned gradually toward the initial value. The area under the concentration/time curve was from 2 to 8 times smaller (P less than 0.002) in the patients with liver disease. To assess possible mechanisms of this change, 5 mg of PLP were intravenously administered to the various patient groups and the pharmacokinetics of the disposition were assessed. The initial and steady state volumes of distribution of PLP were comparable in cirrhotics and controls (P greater than 0.05), but the clearance of plasma PLP in cirrhotics was much faster (63.0 +/- 7.4 versus 31.7 +/- 2.7 ml per min, P less than 0.004). Similar findings were obtained in the other liver disease subjects. The in vitro plasma binding of PLP at supracirculatory concentrations was comparable in cirrhotics and controls (99.4 versus 99.5%, P greater than 0.05).
(1) plasma PLP regulation in patients with liver disease is abnormal, (2) a significant factor in the decrease in plasma PLP after intravenous pyridoxine administration in these patients appears to be an increase in the total plasma clearance of the coenzyme, and (3) it is postulated that this may be due to increased degradation of PLP by the diseased liver.
磷酸吡哆醛（PLP）是维生素B6的辅酶形式，对体内许多生化反应至关重要。对实验动物的研究表明，肝脏是血浆中循环的PLP形成的主要部位，并且它也可能参与其降解。本研究首次评估了人类肝脏疾病对血浆PLP调节的影响。对酒精性肝硬化、急性肝炎和肝外梗阻患者以及正常对照受试者快速静脉注射50mg吡哆醇之前和之后依次测量血浆PLP水平。肝硬化患者的基线血浆PLP浓度显著低于正常人（P＜0.025），肝外梗阻患者有降低的趋势。给予吡哆醇后，血浆PLP水平在2至12小时内显著升高，之后浓度逐渐恢复到初始值。肝病患者的浓度/时间曲线下面积小2至8倍（P＜0.002）。为了评估这种变化的可能机制，对不同患者组静脉注射5mg PLP并评估处置的药代动力学。PLP的初始和稳态分布容积在肝硬化患者和对照组中相当（P＞0.05），但肝硬化患者血浆PLP的清除率快得多（63.0±7.4对31.7±2.7ml/分钟，P＜0.004）。在其他肝病受试者中也获得了类似的结果。在超循环浓度下，PLP的体外血浆结合在肝硬化患者和对照组中相当（99.4对99.5%，P＞0.05）。
（1）肝病患者的血浆PLP调节异常，（2）这些患者静脉注射吡哆醇后血浆PLP降低的一个重要因素似乎是辅酶的总血浆清除率增加，（3）据推测，这可能是由于患病肝脏对PLP的降解增加所致。
