A mathematical model of the kinetics and tissue distribution of 2-fluoro-β-alanine, the major catabolite of 5-fluorouracil

Zhang Ruiwen, Liu Tiepu, Soong Seng-Jaw, Robert B. Diasio

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

2-Fluoro-ß-alanine (FBAL) is the major metabolite of 5-fluorouracil (FUra), one of the most widely used anticancer drugs. It has been suggested previously that FBAL and/or its metabolites may have a role in the hepatotoxidty, neurotoxicity and cardiotoxicity resulting from FUra chemotherapy. Studies in patients and experimental animals have demonstrated that FBAL has a prolonged elimination compared with the parent drug, FUra. In the present manuscript, a mathematical model is developed for the kinetics and tissue distribution of FBAL. This model is based on recently published data from a study of the pharmacokinetics and disposition of FBAL in rats (Zhang et al., Drug Metab Dispos 20: 113-119,1992). Satisfactory agreement was achieved between predicted and measured values, permitting an accurate evaluation of the kinetic and distribution parameters for FBAL. This model indicates that: (1) FBAL accumulates in several tissues including brain, heart, spleen, and enterohepatic system; and (2) enterohepatic circulation of FBAL and its bile add conjugates has an important role in FBAL kinetics and distribution as demonstrated by a model in which enterohepatic circulation parameters were deleted.

Original languageEnglish (US)
Pages (from-to)2063-2069
Number of pages7
JournalBiochemical Pharmacology
Volume45
Issue number10
DOIs
StatePublished - Apr 25 1993

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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