吉西他滨在非小细胞肺癌患者中的药代动力学：79A>C 胞苷脱氨酶多态性的影响。
Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: impact of the 79A>C cytidine deaminase polymorphism.
机构信息
Department of Pharmacy, Diaconessen Hospital Meppel & Bethesda Hospital Hoogeveen, Hoogeveenseweg 38, 7943 KA, Meppel, The Netherlands.
出版信息
Eur J Clin Pharmacol. 2010 Jun;66(6):611-7. doi: 10.1007/s00228-010-0799-0. Epub 2010 Mar 6.
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.
目的
研究胞苷脱氨酶（CDA）基因 79A>C 多态性对非小细胞肺癌（NSCLC）患者吉西他滨及其代谢物 2',2'-二氟脱氧尿苷（dFdU）药代动力学的影响。
患者和方法
20 例患者接受吉西他滨 1125mg/m²作为静脉输注 30 分钟的治疗，用于治疗 NSCLC。在吉西他滨给药后 0-6 小时采集血浆样本。通过高效液相色谱法（HPLC）和紫外检测法定量检测吉西他滨和 dFdU。采用 PCR 和 DNA 测序法确定 CDA 79A>C 基因型。
结果
吉西他滨从血浆中迅速清除，3 小时后无法检测到。79A>C 多态性的等位基因频率为 0.40。二倍型分布为 A/A n = 8，A/C n = 8，和 C/C n = 4。在不同 CDA 基因型与吉西他滨或 dFdU AUC、清除率或半衰期之间未发现显著差异。
结论
CDA 基因的 79A>C 多态性对吉西他滨药代动力学没有重大一致和显著影响。
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