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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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Abbreviations

A i :

coefficient

a i :

exponent

\(\tilde C_p^{iv} \)(s):

Laplace transform of the time course of plasma following intravenous dose

\(\tilde C_p^{po} \)(s):

Laplace transform of the time course of plasma following oral administration dose

\(\tilde C_p^1 \)(s):

Laplace transform of the time course of plasma concentration without EHC

CLb :

clearance into the bile

CL1 :

total clearance through the single EHC (=CLb/Fb)

Div :

intravenous dose

Dpo :

oral administration dose

Fa :

recovery (availability) from intestinal tract to systemic circulation

Fb :

recovery from systemic circulation to intestinal tract

F′a :

recovery from oral dose (absolute availability)

Fc :

recovery through a single pass of EHC

Fg :

recovery through the stomach

\(\tilde f_a \)(s):

transfer function corresponding to the process outside the body through the intestinal tract

\(\tilde f_a^\prime \)(s):

transfer function for oral dose

\(\tilde f_b \)(s):

transfer function through the systemic circulation into the bile

\(\tilde f_c \)(s):

transfer function for a single pass of EHC

\(\tilde f_g \)(s):

transfer function through the stomach

fi(t):

weight function for the processi

\(\tilde f_i \)(s):

Laplace transform off t (t)

\(\tilde f_r \)(s):

transfer function corresponding to the recirculatory process

ka :

absorption rate constant

s :

Laplace variable

\(\bar t_a \) :

mean transit time for the absorption process from the intestinal tract

\(\bar t_a^\prime \) a :

mean transit time for oral dose (=MAT)

\(\bar t_b \) :

mean transit time for the disposition process in the body

\(\bar t_c \) :

mean transit time for a single pass of EHC

t 0 :

gap time

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Authors and Affiliations

  1. Faculty of Pharmaceutical Science, Kyoto University, Sakyo-ku, 606, Kyoto, Japan

    Kiyoshi Yamaoka, Masaharu Kanba, Yoko Toyoda, Yoshitaka Yano & Terumichi Nakagawa

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  1. Kiyoshi Yamaoka
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  2. Masaharu Kanba
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  3. Yoko Toyoda
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  4. Yoshitaka Yano
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  5. Terumichi Nakagawa
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Yamaoka, K., Kanba, M., Toyoda, Y. et al. Analysis of enterohepatic circulation of cefixime in rat by fast inverse Laplace transform (FILT). Journal of Pharmacokinetics and Biopharmaceutics 18, 545–559 (1990). https://doi.org/10.1007/BF01073938

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  • DOI: https://doi.org/10.1007/BF01073938

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