Kurz H, Michels H, Stickel H H
Eur J Clin Pharmacol. 1977 Jul 19;11(6):469-72. doi: 10.1007/BF00562941.
The binding of certain drugs to isolated fractions of plasma proteins obtained from newborn and adult man has been studied by equilibrium dialysis. For thiopental, desipramine, nitrofurantoin, sulfamethoxydiazine, meticillin and salicylic acid no difference was found between binding to the albumin fraction from newborns and adults. However, for thiopental, desipramine and promethazine binding to the globulin fraction was smaller in the newborns than in adults. Addition of bilirubin to the albumin fraction decreased the binding of nitrofurantoin, sulfamethoxydiazine and meticillin. No difference in the binding of meticillin to the albumin or globulin fractions from newborns and adults was found. The binding decreased, however, if both fractions were combined. Four mechanisms to explain the difference in binding between newborns and adults are discussed: (1) Displacement of drugs by bilirubin, (2) different binding properties of cord and adult albumin, (3) different properties of the globulins and (4) interaction of albumin with globulins in the newborn.
通过平衡透析研究了某些药物与从新生儿和成年人获得的血浆蛋白分离组分的结合情况。对于硫喷妥钠、地昔帕明、呋喃妥因、磺胺甲氧嗪、甲氧西林和水杨酸,发现其与新生儿和成年人白蛋白组分的结合没有差异。然而,对于硫喷妥钠、地昔帕明和异丙嗪,其与新生儿球蛋白组分的结合比成年人小。向白蛋白组分中添加胆红素会降低呋喃妥因、磺胺甲氧嗪和甲氧西林的结合。未发现新生儿和成年人的白蛋白或球蛋白组分对甲氧西林的结合有差异。然而,如果将两个组分合并,结合会降低。讨论了四种解释新生儿和成年人结合差异的机制:(1)胆红素对药物的置换作用;(2)脐带血白蛋白和成人白蛋白不同的结合特性;(3)球蛋白的不同特性;(4)新生儿中白蛋白与球蛋白的相互作用。