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.
|Data di pubblicazione:||2002|
|Titolo:||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.|
|Autore/i:||Bocci, G; Danesi, R; Allegrini, G; Innocenti, F; Di Paolo, A; Falcone, A; Conte, Pierfranco; Del Tacca, M.|
|Codice identificativo ISI:||WOS:000180044400005|
|Codice identificativo Scopus:||2-s2.0-0036460047|
|Codice identificativo Pubmed:||12602342|
|Citazione:||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 / Bocci, G; Danesi, R; Allegrini, G; Innocenti, F; Di Paolo, A; Falcone, A; Conte, Pierfranco; Del Tacca, M.. - In: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. - ISSN 0031-6970. - STAMPA. - 58(9)(2002), pp. 593-595.|
|Tipologia||Articolo su rivista|
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