| Toxicokinetic modeling of dose-dependent formate elimination in rats: in vivo-in vitro correlations using the perfused rat liver. | |
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MedLine Citation:
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PMID: 8685905 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The dose-dependent elimination of formate was investigated in the rat using both in vitro and in vivo systems. The in situ perfused liver was used to define the kinetics of hepatic metabolism and obtain initial in vitro estimates of the hepatic metabolism kinetic parameters. Formate was eliminated from the perfused rat liver following Michaelis-Menten kinetics. Estimates of the Michaelis-Menten parameters obtained from the perfused liver studies were used in a two-compartment pharmacokinetic model of the dose-dependent elimination of formate in vivo. This model consisted of a central, well-mixed compartment and a urine compartment. Other features of the model included (1) endogenous production of formate, (2) Michaelis-Menten hepatic metabolism of formate, and (3) renal excretion consisting primarily of glomerular filtration and saturable tubular reabsorption. A good fit of the model to the observed in vivo data was obtained (overall r2 = 0.978). AR dose dependencies of the data could be adequately fitted using a single set of model parameters. Initial estimates of the Michaelis-Menten parameters, Vmax and Km, obtained from the perfused liver system, were within 40% of the final fitted values of these parameters in the in vivo model, indicating the utility of the perfused liver system for performing in vitro-in vivo correlations. |
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Authors:
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P Damian; O G Raabe |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 139 ISSN: 0041-008X ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 1996 Jul |
Date Detail:
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Created Date: 1996-08-21 Completed Date: 1996-08-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 22-32 Citation Subset: IM |
Affiliation:
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Institute of Toxicology and Environmental Health, University of California, Davis 95616, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Absorption Animals Dose-Response Relationship, Drug Formic Acids / pharmacokinetics*, toxicity, urine Glomerular Filtration Rate / physiology Kidney Tubules / metabolism Liver / metabolism* Male Models, Biological Perfusion Rats |
| Chemical | |
Reg. No./Substance:
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0/Formic Acids; 64-18-6/formic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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