Yano Y, Yamaoka K, Aoyama Y, Tanaka H
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
J Pharmacokinet Biopharm. 1989 Apr;17(2):179-202. doi: 10.1007/BF01059027.
A dispersion model developed in chromatographic theory is applied to the analysis of the elution profile in the liver perfusion system of experimental animals. The equation for the dispersion model with the linear nonequilibrium partition between the perfusate and an organ tissue is derived in the Laplace-transformed form, and the fast inverse Laplace transform (FILT) is introduced to the pharmacokinetic field for the manipulation of the transformed equation. By the analysis of the nonlinear least squares method associated with FILT, this model (two-compartment dispersion model) is compared to the model with equilibrium partition between the perfusate and the liver tissue (one-compartment dispersion model) for the outflow curves of ampicillin and oxacillin from the rat liver. The model estimation by Akaike's information criterion (AIC) suggests that the two-compartment dispersion model is more proper than the one-compartment dispersion model to mathematically describe the local disposition of these drugs in the perfusion system. The blood space in the liver, VB, and the dispersion number DN are estimated at 1.30 ml (+/- 0.23 SD) and 0.051 (+/- 0.023 SD), respectively, both of which are independent of the drugs. The efficiency number, RN, of ampicillin is 0.044 (+/- 0.049 SD) which is significantly smaller than 0.704 (+/- 0.101 SD) of oxacillin. The parameters in the two-compartment dispersion model are correlated to the recovery ratio, FH, mean transit time, tH, and the relative variance, sigma 2/t-2H, of the elution profile of drugs from the rat liver.
色谱理论中开发的一种扩散模型被应用于分析实验动物肝脏灌注系统中的洗脱曲线。推导了灌注液与器官组织之间具有线性非平衡分配的扩散模型方程的拉普拉斯变换形式，并将快速逆拉普拉斯变换（FILT）引入药代动力学领域以处理变换后的方程。通过与FILT相关的非线性最小二乘法分析，将该模型（二室扩散模型）与灌注液和肝组织之间具有平衡分配的模型（一室扩散模型）对氨苄青霉素和苯唑西林从大鼠肝脏流出曲线进行比较。基于赤池信息准则（AIC）的模型估计表明，二室扩散模型比一室扩散模型在数学上更适合描述这些药物在灌注系统中的局部处置。肝脏中的血容量VB和扩散数DN分别估计为1.30 ml（±0.23 SD）和0.051（±0.023 SD），两者均与药物无关。氨苄青霉素的效率数RN为0.044（±0.049 SD），明显小于苯唑西林的0.704（±0.101 SD）。二室扩散模型中的参数与大鼠肝脏药物洗脱曲线的回收率FH、平均通过时间tH和相对方差σ2/tH2相关。
