Saitoh Akihiko, Fletcher Courtney V, Brundage Richard, Alvero Carmelita, Fenton Terrence, Hsia Karen, Spector Stephen A
Division of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0672, USA.
J Acquir Immune Defic Syndr. 2007 Jul 1;45(3):280-5. doi: 10.1097/QAI.0b013e318040b29e.
The CYP2B6-G516T polymorphism has been shown to alter plasma efavirenz (EFV) concentrations in adults. The impact of CYP2B6-G516T polymorphisms on EFV concentrations may be different in children because of differences in liver maturation and drug dosage.
The CYP2B6-G516T polymorphisms were analyzed in 71 HIV-1-infected children receiving highly active antiretroviral therapy (HAART) containing EFV for >or=6 months. EFV pharmacokinetics, toxicity profiles, and viral resistance data were also evaluated.
The median oral clearance (CL/F) rate was significantly lower in children with the CYP2B6-516-T/T genotype (3.0 L/h/m2, n=13) than in children with the G/T genotype (5.7 L/h/m2, n=30; P=0.02) or the G/G genotype (7.0 L/h/m2, n=31; P=0.003). In children with the CYP2B6-516-G/G genotype, which is associated with higher expression of hepatic CYP2B6, the clearance rate was significantly higher in younger children (<5 years of age) than in older children (>or=5 years of age) (9.7 L/h/m2 vs. 6.6 L/h/m2; P=0.03). No association was found between CYP2B6-G516T polymorphisms and virologic or immunologic responses, toxicity, or the development of viral resistance against EFV.
CYP2B6-G516T polymorphisms significantly affect the CL/F rate of EFV in children. Changes in hepatic enzyme activity by age may need to be considered when evaluating the impact of genetic variants on antiretroviral pharmacokinetics in children.
CYP2B6-G516T基因多态性已被证明会改变成人血浆中依非韦伦（EFV）的浓度。由于肝脏成熟度和药物剂量的差异，CYP2B6-G516T基因多态性对儿童EFV浓度的影响可能有所不同。
对71名接受含EFV的高效抗逆转录病毒治疗（HAART）≥6个月的HIV-1感染儿童进行CYP2B6-G516T基因多态性分析。还评估了EFV的药代动力学、毒性特征和病毒耐药数据。
CYP2B6-516-T/T基因型儿童（3.0 L/h/m²，n = 13）的口服清除率（CL/F）中位数显著低于G/T基因型儿童（5.7 L/h/m²，n = 30；P = 0.02）或G/G基因型儿童（7.0 L/h/m²，n = 31；P = 0.003）。在与肝脏CYP2B6较高表达相关的CYP2B6-516-G/G基因型儿童中，年龄较小（<5岁）儿童的清除率显著高于年龄较大（≥5岁）儿童（9.7 L/h/m²对6.6 L/h/m²；P = 0.03）。未发现CYP2B6-G516T基因多态性与病毒学或免疫学反应、毒性或对EFV的病毒耐药性发展之间存在关联。
CYP2B6-G516T基因多态性显著影响儿童EFV的CL/F率。在评估基因变异对儿童抗逆转录病毒药代动力学的影响时，可能需要考虑年龄导致的肝酶活性变化。
