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- W3000291205 abstract "ABSTRACT Background Variability in exposure to sorafenib (SO) and sunitinib (SU), two oral tyrosine kinase inhibitors (TKI) approved for the treatment of various solid tumours, is large. Plasma citrulline (CIT) levels reflect the functional small bowel cell mass. We studied the relationship between TKI exposure and intestinal function in adult cancer patients (pts). Methods CIT concentration and drug exposure were determined in 56 pts under SO (n = 38) or SU (n = 18) on day (D) 0 (baseline), then D8 and D22 after treatment initiation. The clinical results led to in vitro studies. In vitro concentration dependent-cytotoxicity of SO and SU was evaluated in Caco-2 cell lines using mitochondrial toxicity test (MTT) assay. Under clinically relevant concentrations of SO (2-10 µg/mL) or SU (0.05-0.10 µg/mL), transepithelial electrical resistance (TEER) and CIT levels at the basolateral side of Caco-2 cells were determined. Results In SO-treated pts, mean citrullinemia on D8 was lower than at D0 (26.2 ± 10.9 mmol/L vs 35.2 ± 13.4, p Conclusions Contrary to SU, SO caused in vitro a cytotoxic effect on Caco-2 cells at therapeutic concentrations. This likely explains the different kinetics of CIT concentrations between SO- and SU-treated pts. Correlation between SO AUC and citrullinemia suggests strongly that functional enterocytic mass contributes to the intra- and inter-individual variability in sorafenib exposure in cancer pts. Disclosure O. Mir: BAYER, PFIZER, ROCHE. F. Goldwasser: BAYER, PFIZER, ROCHE. All other authors have declared no conflicts of interest." @default.
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- W3000291205 date "2012-09-01" @default.
- W3000291205 modified "2023-09-29" @default.
- W3000291205 title "Relationship Between Intestinal Function and Exposure to Sorafenib and Sunitinib in Cancer Patients" @default.
- W3000291205 doi "https://doi.org/10.1016/s0923-7534(20)32797-6" @default.
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