β-内酰胺类抗生素所致中性粒细胞减少症的药代动力学和药物基因组学
Pharmacokinetics and pharmacogenomics of β-lactam-induced neutropenia.
作者信息
Hahn Andrea, Fukuda Tsuyoshi, Hahn David, Mizuno Tomoyuki, Frenck Robert W, Vinks Alexander A
机构信息
Division of Infectious Disease, Children's National Medical Center, Washington, DC 200102, USA.
Department of Pediatrics, George Washington University School of Medicine, Washington, DC 200523, USA.
出版信息
Pharmacogenomics. 2016 Apr;17(6):547-59. doi: 10.2217/pgs-2015-0008. Epub 2016 Apr 5.
AIM
Determine if individuals with β-lactam induced neutropenia have polymorphisms that impair function of MRP4 or OAT1/OAT3.
METHODS
Subjects with β-lactam induced neutropenia were compared to controls for the presence of MRP4 and OAT1/OAT3 polymorphisms, estimated plasma trough concentrations and area under the curve.
RESULTS
Subjects with a homozygous polymorphism at MRP4 3348 A to G were 5.3 times more likely to develop neutropenia (p = 0.171). No statistical differences were noted in pharmacokinetic parameters. Contingency analysis of children greater than 5 years of age showed neutropenia in subjects who were homozygous wild type at MRP4 3348 A to G was significantly associated with standard or high dosing (p = 0.03).
CONCLUSION
MRP4 3348 A to G should be further studied for potential contribution to the development of β-lactam induced neutropenia.
目的
确定β-内酰胺诱导的中性粒细胞减少症患者是否存在损害多药耐药相关蛋白4（MRP4）或有机阴离子转运体1/3（OAT1/OAT3）功能的多态性。
方法
将β-内酰胺诱导的中性粒细胞减少症患者与对照组比较MRP4和OAT1/OAT3多态性的存在情况、估计的血浆谷浓度和曲线下面积。
结果
MRP4 3348 A至G位点存在纯合多态性的患者发生中性粒细胞减少症的可能性高5.3倍（p = 0.171）。药代动力学参数未发现统计学差异。对5岁以上儿童的列联分析显示，MRP4 3348 A至G位点为纯合野生型的患者发生中性粒细胞减少症与标准剂量或高剂量显著相关（p = 0.03）。
结论
应进一步研究MRP4 3348 A至G对β-内酰胺诱导的中性粒细胞减少症发生的潜在作用。
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