Bengtsson B, Bredberg U, Luthman J
Department of Cattle and Sheep Diseases, Swedish University of Agricultural Sciences, Uppsala.
J Vet Pharmacol Ther. 1992 Jun;15(2):202-16. doi: 10.1111/j.1365-2885.1992.tb01008.x.
A mathematical model based on Fick's laws of diffusion describing the concentration of drug in tissue cage models was elaborated. The model takes into account differences in protein binding, tissue cage geometry and serum pharmacokinetics. The validity of the model was tested against experimental data obtained from a tissue cage model in calves by simultaneous fitting to serum and tissue cage fluid (TCF) data in a non-linear least-squares regression computer program. Concentrations of penicillin-G (pen-G) in serum and TCF following intravenous (i.v.) administration of potassium pen-G were adequately described by the mathematical model. Concentrations in TCF after intramuscular (i.m.) administration of the same drug and of procaine pen-G could be predicted by the mathematical model. Concentrations of oxytetracycline (OTC) in serum and TCF following i.v. administration and continuous i.v. infusions were also adequately described by the model, and TCF concentrations after i.m. administration of the same drug could be roughly predicted. The results indicate that pen-G and OTC have the same permeability coefficient for transport from serum to TCF.
构建了一个基于菲克扩散定律的数学模型,用于描述组织笼模型中药物的浓度。该模型考虑了蛋白质结合、组织笼几何形状和血清药代动力学的差异。通过在非线性最小二乘回归计算机程序中同时拟合血清和组织笼液(TCF)数据,根据从犊牛组织笼模型获得的实验数据对模型的有效性进行了检验。数学模型充分描述了静脉注射青霉素G钾后血清和TCF中青霉素G(pen-G)的浓度。该数学模型可以预测同一药物和普鲁卡因青霉素G肌肉注射后TCF中的浓度。该模型也充分描述了静脉注射和持续静脉输注后血清和TCF中土霉素(OTC)的浓度,并且可以大致预测同一药物肌肉注射后TCF中的浓度。结果表明,pen-G和OTC从血清转运到TCF的渗透系数相同。