High inter- and intrapatient variation in 5-fluorouracil plasma concentrations during a prolonged drug infusion

Chris H. Takimoto, Lorrin K. Yee, David J. Venzon, Barbara Schuler, Frank Grollman, Chetin Chabuk, J. Michael Hamilton, Alice P. Chen, Carmen J. Allegra, Jean L. Grem

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Abstract

The purpose of the study was to examine inter- and intrapatient variation in 5-fluorouracil (5-FU) plasma concentrations in adult cancer patients receiving a 3-day drug infusion. Fourteen patients received 1266 mg/m2 N-(phosphonacetyl)-L-aspartate (PALA) infused i.v. over 15 min on day 1, followed immediately by a loading dose of 500 mg/m2 calcium leucovorin over 30 min. Then a prolonged infusion of leucovorin at 500 mg/m2/day and 5- FU at 1750 mg/m2/day was administered as either a constant rate or as a circadian infusion over 72 h. During constant rate infusions, 5-FU concentrations within individuals varied by 1.7-fold, but no uniform time of peak or trough concentration was observed. Transformation of these data by setting the time of peak to 0 h and by expressing concentrations as the percentage of the 24-h mean value revealed a nonrandom distribution of the time from peak to trough with a median time of 12 h (P = 0.027). These transformed data were also successfully fit to a circadian cosinor function (P < 0.001). During multiple constant rate 5-FU infusions, the intrapatient variability was high; the times of peak 5-FU concentration occurred at the same approximate sampling time 43% of the time, and troughs coincided 17% of the time. No difference in clinical toxicity was observed when matched constant rate and circadian infusions of 5-FU were compared. High inter- and intrapatient variability exists in 5-FU plasma concentrations in adult cancer patients during constant rate infusions with no evidence of a consistent circadian rhythm in untransformed data.

Original languageEnglish (US)
Pages (from-to)1347-1352
Number of pages6
JournalClinical Cancer Research
Volume5
Issue number6
Publication statusPublished - Jun 1 1999

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Takimoto, C. H., Yee, L. K., Venzon, D. J., Schuler, B., Grollman, F., Chabuk, C., ... Grem, J. L. (1999). High inter- and intrapatient variation in 5-fluorouracil plasma concentrations during a prolonged drug infusion. Clinical Cancer Research, 5(6), 1347-1352.