伏立康唑抗真菌药物在儿科患者中的遗传药理学。
Pharmacogenetic of voriconazole antifungal agent in pediatric patients.
机构信息
Department of Medical Sciences, University of Turin - ASL 'Città di Torino', Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Turin, Italy.
Department of Biological & Clinical Sciences, University of Turin, S Luigi Gonzaga Hospital, Orbassano, 10043 Turin, Italy.
出版信息
Pharmacogenomics. 2018 Jul 1;19(11):913-925. doi: 10.2217/pgs-2017-0173. Epub 2018 Jun 19.
AIM
We explored the role of SNPs within the SLCO1B3, SLCO1B1, SLC22A6, ABCB1, ABCG2, SLCO3A1, CYP2C19, ABCC2, SLC22A1, ABCB11 and NR1I2 genes on voriconazole pharmacokinetics.
PATIENTS & METHODS: 233 pediatric patients were enrolled. Drug plasma C was measured by a HPLC-MS method. Allelic discrimination was performed by qualitative real-time PCR.
RESULTS
SLCO1B3 rs4149117 c.334 GT/TT (p = 0.046), ABCG2 rs13120400 c.1194 + 928 CC (p = 0.029) and ABCC2 rs717620 c.-24 GA/AA (p = 0.025) genotype groups significantly influenced C. ethnicity (p = 0.042), sex (p = 0.033), SLCO1B3 rs4149117 c.334 GT/TT (p = 0.041) and ABCB1 rs1045642 c.3435 TT (p = 0.016) have been retained in linear regression model as voriconazole predictor factors.
CONCLUSION
Understanding how some gene polymorphisms affect the voriconazole pharmacokinetic is essential to optimally dose this agent.
目的
我们探讨了 SLCO1B3、SLCO1B1、SLC22A6、ABCB1、ABCG2、SLCO3A1、CYP2C19、ABCC2、SLC22A1、ABCB11 和 NR1I2 基因内的 SNPs 对伏立康唑药代动力学的作用。
患者和方法
共纳入 233 例儿科患者。采用 HPLC-MS 法测定药物血浆 C。通过定性实时 PCR 进行等位基因鉴别。
结果
SLCO1B3 rs4149117 c.334 GT/TT（p=0.046）、ABCG2 rs13120400 c.1194+928 CC（p=0.029）和 ABCC2 rs717620 c.-24 GA/AA（p=0.025）基因型组显著影响 C。种族（p=0.042）、性别（p=0.033）、SLCO1B3 rs4149117 c.334 GT/TT（p=0.041）和 ABCB1 rs1045642 c.3435 TT（p=0.016）在线性回归模型中作为伏立康唑预测因子保留。
结论
了解某些基因多态性如何影响伏立康唑的药代动力学对于最佳剂量该药物至关重要。
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