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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Does saturable formation of gemcitabine triphosphate occur in patients?

AIM: This study aims to determine if intracellular formation of gemcitabine triphosphate (dFdCTP), an active metabolite of gemcitabine, is saturable at doses used for treatment of Asian patients with lung cancer. METHODS: From a phase II trial, plasma concentrations of gemcitabine, its inactive metabolite 2'-2'-difluorodeoxyuridine (dFdU), and mononuclear cell concentrations of gemcitabine-triphosphate were measured in 56 and 33 patients, respectively. The pharmacokinetics of gemcitabine and metabolites were modeled using nonlinear mixed effects modeling (NONMEM). A reduced dataset of ten randomly selected patients was employed to compare first-order and saturable formation of dFdCTP from gemcitabine. RESULTS: The median population clearance estimate for dFdCTP formation with the full dataset was 70.2 L/h/70 kg/1.7 m. Modeling Michaelis-Menten formation of dFdCTP on a reduced dataset estimated K(m) to be 3.6 times higher than the maximum gemcitabine concentration (72.2 microM) measured in this study. CONCLUSIONS: The results showed that first-order and nonsaturable clearance described intracellular dFdCTP formation at clinically applied doses of gemcitabine.[1]

References

  1. Does saturable formation of gemcitabine triphosphate occur in patients? Tham, L.S., Wang, L.Z., Soo, R.A., Lee, H.S., Lee, S.C., Goh, B.C., Holford, N.H. Cancer Chemother. Pharmacol. (2008) [Pubmed]
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