Document Detail

Measurement of in vitro cellular pharmacokinetics of 5-fluorouracil in human and rat cancer cell lines and rat hepatocytes using a flow-through system.
MedLine Citation:
PMID:  1998989     Owner:  NLM     Status:  MEDLINE    
A flow-through system was used to study the cellular pharmacokinetics of 5-fluorouracil (5-FU) in four human cell lines (squamous-cell carcinoma HEp-2, colon carcinoma WiDr, hepatoma Hep G2, and breast carcinoma MCF-7) as well as in the rat hepatoma H35 cell line and in freshly isolated rat hepatocytes. The system made it possible to restrict the decrease in the concentration of 5-FU in the medium, to keep the volume in which the metabolites accumulated relatively small, and to study the dynamics of a response during and after a change in the composition of the eluent. Clearance of 5-FU from the eluent was achieved predominantly (greater than 95%) by its catabolism to dihydrofluorouracil in the tumor cell lines and to 2-fluoro-beta-alanine in the hepatocytes. Not only rat hepatocytes but also HEp-2 cells showed relatively high clearance values. A concentration-dependent 5-FU elimination was observed, indicating saturation of 5-FU elimination according to Michaelis-Menten kinetics (Km 14-22 microM). The maximal velocity (Vmax) values ranged from 0.025 to 0.13 nmol 5-FU/10(6) cells per minute. For HEp-2 cells, high-concentration pulse injections of 5-FU, thymine, uridine, or uracil immediately led to a reduction in 5-FU conversion, followed by recovery within 5 min. The flow-through system proved to be adequate for the study of the non-linear pharmacokinetics of 5-FU in different intact cells and for the comparison of various manipulations of these pharmacokinetics.
E C Spoelstra; H M Pinedo; H Dekker; G J Peters; J Lankelma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  27     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  1991  
Date Detail:
Created Date:  1991-04-05     Completed Date:  1991-04-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  320-5     Citation Subset:  IM    
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
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MeSH Terms
Dose-Response Relationship, Drug
Fluorouracil / pharmacokinetics*
Liver / metabolism*
Metabolic Clearance Rate
Tumor Cells, Cultured / metabolism
Reg. No./Substance:

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