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/m(2) 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.

• Authors: Jan Gerard Maring, Floris M Wachters, Monique Slijfer, J Marina Maurer, H Marike Boezen, Donald R A Uges, Elisabeth G E de Vries, Harry J M Groen
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 66 Issue 6 Pg. 611-7 (Jun 2010) ISSN: 1432-1041 [Electronic] Germany
• PMID: 20213492 (Publication Type: Clinical Trial, Phase III, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Floxuridine
• Deoxycytidine
• Cytidine Deaminase
• 2',2'-difluoro-2'-deoxyuridine
• Gemcitabine

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (administration & dosage, pharmacokinetics)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (blood, drug therapy)
• Cytidine Deaminase (genetics)
• Deoxycytidine (administration & dosage, analogs & derivatives, pharmacokinetics)
• Female
• Floxuridine (analogs & derivatives, pharmacokinetics)
• Gene Frequency
• Genotype
• Humans
• Lung Neoplasms (blood, drug therapy)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Polymorphism, Single Nucleotide
• Gemcitabine