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Influence of age on pharmacokinetics of capecitabine and its metabolites in older adults with cancer: a pilot study.
- Source :
-
Cancer Chemotherapy & Pharmacology . Aug2023, Vol. 92 Issue 2, p135-139. 5p. - Publication Year :
- 2023
-
Abstract
- Background: Capecitabine is an oral chemotherapy prodrug of 5-fluorouracil (5-FU) with unpredictable toxicity, especially in older adults. The aim of this study was to evaluate the pharmacokinetics (PK) of capecitabine and its metabolites in younger adults (< 70 years) and older adults (≥ 70 years) receiving capecitabine for solid cancer. Methods: Eligible participants receiving capecitabine had 2 venous samples collected on day 14 of cycle 1 and cycle 2 of their treatment. Capecitabine and metabolite concentrations were determined using liquid chromatography with tandem mass spectrometry. A Bayesian estimation approach was used to generate individual estimates of PK parameters for 5-FU. A linear mixed-effect analysis of variance (ANOVA) model was used to compare dose-normalised log-transformed PK parameters between age groups. Correlations were determined by linear regression and logistic regression analyses. Results: Of the total 26 participants, 58% were male with a median age of 67 years (range, 37–85) with 54% aged < 70 years and 46% aged ≥ 70 years. Participants aged ≥ 70 years, compared to those aged < 70 years, had a greater 5-FU exposure based on area under the concentration–time curve (AUC) of 17% (90% CI 103–134%; 0.893 vs. 0.762 mg h/L) and 14% increase in maximal concentration, Cmax (90% CI 82.1–159%; 0.343 vs. 0.300 mg/L). The 5-FU Cmax was positively associated with time up and go (TUG) (Pearson's correlation 0.77, p = 0.01), but not other geriatric assessment domains or severe toxicity. Conclusion: 5-FU exposure was significantly increased in older adults compared to younger adults receiving equivalent doses of capecitabine, and is a possible cause for increased toxicity in older adults. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03445704
- Volume :
- 92
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cancer Chemotherapy & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 164752063
- Full Text :
- https://doi.org/10.1007/s00280-023-04552-5