Evaluation of Capacity-limited First-pass Effect Through Liver by Three-points Sampling in Portal and Hepatic Veins and Systemic Artery

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2002 Jul 24

PMID 12134957

Citations 2

Authors

Shinya Ueda

Kiyoshi Yamaoka

Jyoji Yui

Akio Shigematsu

Terumichi Nakagawa

Affiliations

Soon will be listed here.

Abstract

Purpose: The three-points method was newly developed by sampling the portal and hepatic veins and systemic artery. A model of hepatic local disposition with the Michaelis-Menten elimination was proposed to explain the concentration dependency of the hepatic recovery ratio (F(H)).

Methods: 5-fluorouracil (5-FU) was selected as a model drug. 5-FU was administered orally 90 min after its intraarterial dose. Blood specimens in both femoral artery and hepatic vein were sampled after intraarterial dose, and blood specimens in both femoral artery and portal vein were taken after oral administration.

Results: It was shown that F(H) increased with an increase in the input drug concentration into the liver. The mean absorption time (MAT) estimated by nonlinear analysis agreed with the mean local absorption time (t(n)) whereas MAT by linear analysis was significantly smaller than t(a).

Conclusions: The three-points method was newly developed, and the proposed nonlinear model explained well the capacity-limited elimination of 5-FU through the liver. MAT by the nonlinear analysis was in good agreement with t(a).

Citing Articles

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Yasui H, Adachi Y, Katoh A, Sakurai H J Biol Inorg Chem. 2007; 12(6):843-53.

PMID: 17503093 DOI: 10.1007/s00775-007-0239-5.

Mean hepatic recovery ratio in capacity-limited first-pass effect by three-point sampling method.

Higashimori M, Yamaoka K J Pharmacokinet Pharmacodyn. 2003; 30(4):309-13.

PMID: 14650376 DOI: 10.1023/a:1026146802731.

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