Severe 5-fluorouracil toxicity associated with a marked alteration of pharmacokinetics of 5-fluorouracil and its catabolite 5-fluoro-5,6-dihydrouracil: a case report

Eur J Clin Pharmacol. 2002 Dec;58(9):593-5. doi: 10.1007/s00228-002-0534-6.


Objective: To describe the altered pharmacokinetics of 5-fluorouracil (5-FU) and its major catabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) in a 52-year-old woman affected by a severe 5-FU toxicity.

Methods: Toxicities were rated according to World Health Organization. 5-FU and 5-FDHU plasma concentrations and dihydropyrimidine dehydrogenase (DPD) activity of peripheral blood mononuclear cells (PBMC) were measured by HPLC analysis.

Results: After a single cycle of 5-FU therapy the patient developed grade 4 diarrhea and stomatitis, grade 3 vomiting, neutropenia, and dermatitis. Compared to a control population, 5-FU AUC, elimination half-life, and C(max) were markedly increased (24.75 vs. 9.25 +/- 0.63 h microg/ml, >5 vs. 0.36 +/- 0.05 h, and 58.54 vs. 37.2 +/- 4.03 microg/ml, respectively) whereas systemic clearance was decreased (12 vs. 51.29 +/- 2.97 l/h/m2); also 5-FDHU AUC (3.3 vs. 12.35 +/- 0.7 h microg/ml) and C(max) (3.4 vs. 4.56 +/- 0.15 microg/ml), which was reached with delay, were reduced. Surprisingly, the PBMC DPD activity (110.8 pmol/min/mg protein) and urinary uracil (68.32 micromol/g urinary creatinine) were within normal range.

Conclusions: Our results show the altered 5-FU and 5-FDHU pharmacokinetics in a severe 5-FU toxicity case due to an impairment of the hepatic DPD activity and suggest the necessity of a pharmacological evaluation of 5-FU treated patients.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia / chemically induced
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Area Under Curve
  • Diarrhea / chemically induced
  • Drug Eruptions / etiology
  • Female
  • Fever / chemically induced
  • Fluorouracil / adverse effects*
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / blood
  • Fluorouracil / pharmacokinetics
  • Humans
  • Middle Aged
  • Neutropenia / chemically induced
  • Stomatitis / chemically induced
  • Vomiting / chemically induced


  • Antimetabolites, Antineoplastic
  • 5-fluorodihydrouracil
  • Fluorouracil