Yamaoka K, Kanba M, Toyoda Y, Yano Y, Nakagawa T
Faculty of Pharmaceutical Science, Kyoto University, Japan.
J Pharmacokinet Biopharm. 1990 Dec;18(6):545-59. doi: 10.1007/BF01073938.
The enterohepatic circulation of cefixime in rat was evaluated by a nonlinear least square analysis program, MULTI(FILT), into which the fast inverse Laplace transform (FILT) was incorporated. The plasma time course in the bile duct-cannulated rat exhibited a biexponential curve after the rapid iv administration of cefixime. Several pharmacokinetic models for the enterohepatic circulation were constructed based on the recirculatory concept and the Laplace-transformed equations corresponding to these models were derived by means of the method of transfer function. The transformed equations were simultaneously fitted to the time courses of plasma concentration in rats with laparotomy and with bile duct cannula. The optimum model was selected based on the Akaike's information criterion (AIC). The local moment characteristics for a single pass through enterohepatic circulation were further calculated from the time courses of both the plasma concentration and the amount excreted into the bile. The recovery ratio (Fc) and the mean circulatory time (-tc) through a single pass of enterohepatic circulation were estimated 27.9% and 1.07 hr, respectively. The recovery ratio (Fa) and the mean absorption time (-tc) for the absorption process from the intestinal tract into the systemic circulation were 68.3% and 0.0234 hr, respectively. The recovery ratio (Fb) and the mean transit time (-tb) for the disposition process through the systemic circulation into the bile were 40.8% and 1.05 hr, respectively.
通过纳入快速拉普拉斯逆变换（FILT）的非线性最小二乘分析程序MULTI(FILT)评估了头孢克肟在大鼠体内的肠肝循环。在快速静脉注射头孢克肟后，胆管插管大鼠的血浆时间进程呈现出双指数曲线。基于再循环概念构建了几种肠肝循环的药代动力学模型，并通过传递函数法推导了与这些模型相对应的拉普拉斯变换方程。将变换后的方程同时拟合到开腹大鼠和胆管插管大鼠的血浆浓度时间进程。根据赤池信息准则（AIC）选择最佳模型。从血浆浓度和胆汁排泄量的时间进程进一步计算单次通过肠肝循环的局部矩特征。单次通过肠肝循环的回收率（Fc）和平均循环时间（-tc）分别估计为27.9%和1.07小时。从肠道吸收进入体循环过程的回收率（Fa）和平均吸收时间（-tc）分别为68.3%和0.0234小时。从体循环进入胆汁的处置过程的回收率（Fb）和平均转运时间（-tb）分别为40.8%和1.05小时。
