Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: Impact of the 79A>C cytidine deaminase polymorphism

Abstract

Objective: To study the impact of the 79A>C polymorphism in the cytidine deaminase (CDA) gene on the pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in non-small-cell lung cancer (NSCLC) patients. Patients and methods: Patients (n=20) received gemcitabine 1,125 mg/m2 as a 30 min i.v. infusion as part of treatment for NSCLC. Plasma samples were collected during 0-6 h after gemcitabine administration. Gemcitabine and dFdU were quantified by high performance liquid chromatography with ultraviolet detection. The CDA 79A>C genotype was determined with PCR and DNA sequencing. Results: Gemcitabine was rapidly cleared from plasma and undetectable after 3 h. The allele frequency of the 79A>C polymorphism was 0.40. Diplotypes were distributed as A/A n=8, A/C n=8,and C/C n=4. No significant differences were found between the different CDA genotypes and gemcitabine or dFdU AUC, clearance, or half-life. Conclusion: The 79A>C polymorphism in the CDA gene does not have a major consistent and signficant impact on gemcitabine pharmacokinetics. © 2010 Springer-Verlag.