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Journal of Pharmacokinetics and Biopharmaceutics

, Volume 18, Issue 6, pp 545–559 | Cite as

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

  • Kiyoshi Yamaoka
  • Masaharu Kanba
  • Yoko Toyoda
  • Yoshitaka Yano
  • Terumichi Nakagawa
Article

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 (Fcand the mean circulatory time (¯tcthrough a single pass of enterohepatic circulation were estimated 27.9% and 1.07 hr, respectively. The recovery ratio (Faand the mean absorption time (¯tafor the absorption process from the intestinal tract into the systemic circulation were 68.3% and 0.0234 hr, respectively. The recovery ratio (Fband the mean transit time (¯tb)for the disposition process through the systemic circulation into the bile were 40.8% and 1.05hr, respectively.

Key words

enterohepatic circulation recirculatory pharmacokinetics cefixime AIC FILT local moment global moment 

Notation

Ai

coefficient

ai

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

t0

gap time

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Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Kiyoshi Yamaoka
    • 1
  • Masaharu Kanba
    • 1
  • Yoko Toyoda
    • 1
  • Yoshitaka Yano
    • 1
  • Terumichi Nakagawa
    • 1
  1. 1.Faculty of Pharmaceutical ScienceKyoto UniversityKyotoJapan

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