Concentration-dependent disappearance of fluorouracil from peritoneal fluid in the rat: experimental observations and distributed modeling

The rate of disappearance of fluorouracil from peritoneal fluid has been experimentally measured and mathematically modeled. The experimental data were obtained following the instillation of 50 ml of dialysis fluid which contained an initial fluorouracil concentration ranging from 24 microM to 12 mM...

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Bibliographic Details
Published inJournal of pharmaceutical sciences Vol. 71; no. 7; p. 735
Main Authors Collins, J M, Dedrick, R L, Flessner, M F, Guarino, A M
Format Journal Article
LanguageEnglish
Published United States 01.07.1982
Subjects
Animals
Ascitic Fluid - metabolism
Diffusion
Female
Fluorouracil - metabolism
Models, Biological
Rats
Rats, Inbred Strains
Time Factors
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Summary:The rate of disappearance of fluorouracil from peritoneal fluid has been experimentally measured and mathematically modeled. The experimental data were obtained following the instillation of 50 ml of dialysis fluid which contained an initial fluorouracil concentration ranging from 24 microM to 12 mM. The rate of disappearance was strongly dependent upon concentration. A distributed model has been formulated which incorporates concepts of diffusion with saturable metabolism and nonsaturable capillary uptake in the tissue surrounding the peritoneal fluid. This model successfully describes the experimental observations and also suggests that the effective penetration depth into tissue is highly dependent upon concentration.
ISSN:0022-3549
DOI:10.1002/jps.2600710704