Kanamori T, Takeshita T, Sakai K
Department of Chemical Engineering, Waseda University, Tokyo, Japan.
Biotechnol Prog. 1996 Jul-Aug;12(4):503-9. doi: 10.1021/bp960036o.
The removal rate of a drug by a hemodialyzer is very important to determine the dosage of the drug to a patient without kidney function. Mass transfer of a drug in a hemodialyzer and a patient's body is more complicated than that of ordinary solutes because most drugs are adsorbed by serum albumin. In this paper, we reveal the adsorption characteristics of five clinical antibiotics onto human serum albumin (HSA) with new experimental methods and discuss the influence of adsorption characteristics on removal of antibiotics by hemodialyzers using mathematical models. The adsorption equilibrium of the antibiotics with HSA followed the Langmuir isotherm. Adsorption rates of the antibiotics onto HSA were measured using a constant-flow stirred tank reactor with an ultrafiltration module. A kinetic model for antibiotic transfer in a hemodialyzer and a patient's body was derived with the parameters obtained by the above experiments. Validity of the model was confirmed by dialysis experiments using hemodialyzers and antibiotic solutions including HSA. Removal estimation of a drug by hemodialysis therapy is feasible by the model with the parameters of the Langmuir isotherm for the drug.
血液透析器对药物的清除率对于确定给无肾功能患者使用药物的剂量非常重要。药物在血液透析器和患者体内的传质比普通溶质更为复杂，因为大多数药物会被血清白蛋白吸附。在本文中，我们采用新的实验方法揭示了五种临床抗生素在人血清白蛋白（HSA）上的吸附特性，并使用数学模型讨论了吸附特性对血液透析器清除抗生素的影响。抗生素与HSA的吸附平衡遵循朗缪尔等温线。使用带有超滤模块的恒流搅拌釜反应器测量抗生素在HSA上的吸附速率。利用上述实验获得的参数推导了血液透析器和患者体内抗生素转移的动力学模型。通过使用血液透析器和含HSA的抗生素溶液进行透析实验，证实了该模型的有效性。利用该药物的朗缪尔等温线参数，通过该模型对血液透析治疗中药物的清除进行估算具有可行性。
