SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite disposition in patients with solid tumours
| Autor: | James Fisher, Arkadiusz Z. Dudek, Mark N. Kirstein, Brent W. Williams, Vadim J. Gurvich, Jatinder K. Lamba, Robert A. Kratzke, Edward W Greeno, Richard C. Brundage, Keith M. Skubitz, Amit Khatri, Lev G Lis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cancer Research Antimetabolites Antineoplastic dFdCTP Genotype Metabolite Rate of infusion Pharmacology Deoxycytidine 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine population pharmacokinetic model infusion rate Cytidine Deaminase Neoplasms Medicine Humans In patient Infusions Intravenous 5'-Nucleotidase Alleles 030304 developmental biology Aged pharmacogenomics Aged 80 and over 0303 health sciences business.industry gemcitabine Membrane Transport Proteins Disposition covariates Middle Aged Gemcitabine 3. Good health Oncology chemistry 030220 oncology & carcinogenesis Pharmacogenomics Clinical Study Leukocytes Mononuclear Female business medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: Gemcitabine is used for the treatment of several solid tumours and exhibits high inter-individual pharmacokinetic variability. In this study, we explore possible predictive covariates on drug and metabolite disposition. Methods: Forty patients were enrolled. Gemcitabine and dFdU concentrations in the plasma and dFdCTP concentrations in peripheral blood mononuclear cell were measured to 72 h post infusion, and pharmacokinetic parameters were estimated by nonlinear mixed-effects modelling. Patient-specific covariates were tested in model development. Results: The pharmacokinetics of gemcitabine was best described by a two-compartment model with body surface area, age and NT5C2 genotype as significant covariates. The pharmacokinetics of dFdU and dFdCTP were adequately described by three-compartment models. Creatinine clearance and cytidine deaminase genotype were significant covariates for dFdU pharmacokinetics. Rate of infusion of |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|