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Journal ArticleDOI

Nonlinear pharmacokinetic models for 5-fluorouracil in man: intravenous and intraperitoneal routes.

TLDR
This model has been extended to include intraperitoneal and oral administration of 5FU by the addition of peritoneal fluid and liver compartments and the effect of venous and arterial plasma sampling is discussed.
Abstract
A two-compartment physiologic pharmacokinetic model has been developed for 5-fluorouracil (5FU). This model, which incorporates saturable whole body clearance, satisfactorily predicts disappearance kinetics after an intravenous bolus and steady-state levels during constant intravenous infusions. A half-saturating concentration (KM) of 15 microM was determined by comparison of model simulations with literature data. Both hepatic and extrahepatic elimination can be inferred for 5FU, but the exact anatomic or compartmental location of the clearance cannot be determined from the available clinical data. The effect of venous and arterial plasma sampling is discussed. This model has been extended to include intraperitoneal and oral administration of 5FU by the addition of peritoneal fluid and liver compartments.

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Citations
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Journal ArticleDOI

Clinical pharmacology of 5-fluorouracil.

TL;DR: 5-Fluorouracil, first introduced as a rationally synthesised anticancer agent 30 years ago, continues to be widely used in the management of several common malignancies including cancer of the colon, breast and skin.
Journal ArticleDOI

Fluorouracil: biochemistry and pharmacology.

TL;DR: Biochemical modulation of 5FU metabolism can be applied to overcome resistance against 5FU, and delayed administration of uridine has recently been shown to "rescue" mice and patients from toxicity, while pretreatment with leucovorin is the most promising combination to enhance the therapeutic efficacy.
Journal ArticleDOI

Physiologically based pharmacokinetic modeling: Principles and applications

TL;DR: I was evaluated as a model organic anionic compound by characterizing the pharmacokinetics at three different doses and it was demonstrated that the biliary excretion of I depended on the amount present in the liver, and a saturable uptake process.
Journal ArticleDOI

Extrahepatic Metabolism of Drugs in Humans

TL;DR: The metabolic profile and sites of enzymatic reactions for each drug should be determined and extrahepatic metabolism has been demonstrated for numerous drugs.
Journal ArticleDOI

First-pass elimination. Basic concepts and clinical consequences.

TL;DR: The extent of first-pass metabolism in the liver and intestinal wall depends on a number of physiological factors, including enzyme activity, plasma protein and blood cell binding, and gastrointestinal motility, and models that describe the dependence of bioavailability on changes in these physiological variables have been developed.
References
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Book

Fundamentals of Clinical Pharmacokinetics

TL;DR: In this article, the fundamental principles of clinical pharmacokinetics were discussed. But they did not consider the effects of pharmacokinetic factors on clinical drug development. [2].
Journal Article

A clinical-pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2'-deoxyuridine and 5-fluorouracil.

TL;DR: Hepatic arterial infusion is supported as a means to improve the therapeutic index of FdUrd and fluorouracil in the treatment of cancer in the liver and this type of analytical approach should prove valuable in the evaluation of other agents for liver cancer treatment.
Journal ArticleDOI

RESEARCH ARTICLESMethotrexate Pharmacokinetics

TL;DR: A pharmacokinetic model is presented to predict the detailed distribution and excretion of methotrexate in several mammalian species over a wide range of doses.
Journal Article

The route of absorption of intraperitoneally administered compounds

TL;DR: Results demonstrate that compounds administered i.p. are absorbed primarily through the portal circulation and, therefore, must pass through the liver before reaching other organs.
Journal ArticleDOI

Lidocaine disposition kinetics in monkey and man; I. Prediction by a perfusion model

TL;DR: Blood flow and tissue composition data from monkeys can be applied to man to predict blood levels of lidocaine after intravenous injection and the perfusion model is potentially useful in describing and predicting blood levels in states of cardiovascular disease in both monkey and man.
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