当前位置： SCI文献检索 > BIOLOGICAL & PHARMACEUTICAL BULLETIN期刊下所有文献 > Pharmacokinetic analysis program based on tank-in-series model, MULTI(TIS), for evaluation of capacity-limited local disposition.

Pharmacokinetic analysis program based on tank-in-series model, MULTI(TIS), for evaluation of capacity-limited local disposition.

Abstract：

:A pharmacokinetic analysis program based on a tank-in-series model, MULTI(TIS), was developed for the evaluation of dose-dependency in the local disposition of a drug. The program written in FORTRAN was constructed by expanding MULTI(RUNGE). The reliability of MULTI(TIS) was verified by analyzing the experimental data based on linear and nonlinear tank-in-series models. Linear one- and two-compartment tank-in-series models were adopted to analyze outflow time profiles in single-pass hepatic perfusion following a pulse input of 5'-deoxy-5-fluorouridine (DFUR). The estimated parameters agreed well with those by MULTI(FILT) which is widely used for linear kinetic analysis. The nonlinear models adopted were one-compartment model with Michaelis-Menten elimination and two-compartment models with Michaelis-Menten elimination from central and peripheral compartments. Oxacillin was used as a model drug, because time courses of oxacillin show a capacity-limited hepatic disposition following a pulse input in high doses to the liver (300, 1000, 3000 and 5000 microg). The hepatic recovery ratio (F(H)) of oxacillin increased with dose, whereas the mean transit time (tH) was almost constant. The maximum elimination rate constant (Vmax) and Michaelis constant (Km) of oxacillin were estimated to be 1980 microg/ml/min and 54.1 microg/ml, respectively. Thus, the reliability of MULTI(TIS) was demonstrated for the analysis of nonlinear local disposition, especially, capacity-limited elimination in the liver.

journal_name

Biol Pharm Bull

journal_title

Biological & pharmaceutical bulletin

authors

Fukumura K,Yamaoka K,Higashimori M,Nakagawa T

doi

10.1248/bpb.21.1338

subject

Has Abstract

pub_date

1998-12-01 00:00:00

pages

1338-43

issue

12

eissn

0918-6158

issn

1347-5215

journal_volume

21

pub_type

杂志文章

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