Chamnanphon Monpat, Sukprasong Rattanaporn, Gaedigk Andrea, Manosuthi Weerawat, Chariyavilaskul Pajaree, Wittayalertpanya Supeecha, Koomdee Napatrupron, Jantararoungtong Thawinee, Puangpetch Apichaya, Sukasem Chonlaphat
Department of Pathology, Faculty of Medicine, Srinakharinwirot University, Nakornnayok, Thailand.
Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Pharmgenomics Pers Med. 2021 Jul 24;14:915-926. doi: 10.2147/PGPM.S306358. eCollection 2021.
Plasma efavirenz (EFV) concentrations within therapeutic levels are essential to successfully treat patients suffering from human immunodeficiency virus (HIV) type 1. In addition to the drug-metabolizing enzyme CYP2B6, other phase II drug-metabolizing enzymes and transporters may have an important role in the pharmacokinetics of EFV. Thus, the influence of phase II drug-metabolizing enzymes and drug transporters on plasma EFV levels was investigated in Thai HIV patients receiving EFV.
Genotyping was performed by TaqMan real-time PCR in 149 HIV-infected Thai adults, and plasma efavirenz concentration was measured by a validated high-performance liquid chromatography in 12 hours after dosing steady-state plasma samples at week 12 and 24.
Patients with three or more copies of had significantly lower median plasma EFV concentrations than those carrying two copies at week 12 (=0.046) and (c.638G>A) carriers had significantly lower median plasma EFV concentrations compared to those not carrying the variant at week 24 (=0.048). However, no significant association was found after adjusting for genotype.
Genetic variation in a combination of and copy number may contribute to variability in EFV metabolism and thereby may impact drug response. The influence of a combination between the and genotype on EFV pharmacokinetics should be further investigated in a larger study population.
治疗水平内的血浆依非韦伦（EFV）浓度对于成功治疗1型人类免疫缺陷病毒（HIV）感染患者至关重要。除药物代谢酶CYP2B6外，其他II相药物代谢酶和转运蛋白可能在EFV的药代动力学中起重要作用。因此，在接受EFV治疗的泰国HIV患者中研究了II相药物代谢酶和药物转运蛋白对血浆EFV水平的影响。
对149名感染HIV的泰国成年人进行TaqMan实时PCR基因分型，并在第12周和第24周给药稳态血浆样本后12小时，通过经过验证的高效液相色谱法测量血浆依非韦伦浓度。
在第12周时，携带三个或更多拷贝的患者的血浆EFV中位数浓度显著低于携带两个拷贝的患者（P = 0.046），并且在第24周时，（c.638G>A）携带者的血浆EFV中位数浓度显著低于未携带该变体的患者（P = 0.048）。然而，在调整CYP2B6基因型后未发现显著关联。
UGT2B7和CYP2B6拷贝数组合的基因变异可能导致EFV代谢的变异性，从而可能影响药物反应。应在更大的研究人群中进一步研究UGT2B7和CYP2B6基因型组合对EFV药代动力学的影响。
