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      Association of cyclophosphamide pharmacokinetics to polymorphic cytochrome P450 2C19.

      The Pharmacogenomics Journal
      Adult, Aged, Aryl Hydrocarbon Hydroxylases, genetics, Cyclophosphamide, pharmacokinetics, urine, Cytochrome P-450 CYP2C19, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Mixed Function Oxygenases

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          Abstract

          Cyclophosphamide (CP), a widely used cytostatic, is metabolized by polymorphic drug metabolizing enzymes particularly cytochrome P450 (CYP) enzymes. Its side effects and clinical efficacy exhibit a broad interindividual variability, which might be due to differences in pharmacokinetics. CP-kinetics were determined in 60 patients using a global and a population pharmacokinetic model considering functionally relevant polymorphisms of CYP2B6, CYP2C9, CYP2C19, CYP3A5, and GSTA1. Moreover, metabolic ratios were calculated for selected CP metabolites, analyzed by (31)P-NMR-spectroscopy. Analysis of variance revealed that the CYP2C19*2 genotype influenced significantly pharmacokinetics of CP at doses

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