Analysis of enterohepatic circulation of cefixime in rat by fast inverse Laplace transform (FILT)

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Abstract
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 (¯ta 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 1.05hr, respectively.

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