CYP2C19 弱代谢者的 SLCO2B1 c.*396T>C 基因多态性影响伏立康唑的口服吸收。
Oral absorption of voriconazole is affected by SLCO2B1 c.*396T>C genetic polymorphism in CYP2C19 poor metabolizers.
机构信息
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Department of Clinical Pharmacology and Therapeutics, Hanyang University Seoul Hospital, Seoul, Republic of Korea.
出版信息
Pharmacogenomics J. 2020 Dec;20(6):792-800. doi: 10.1038/s41397-020-0166-1. Epub 2020 May 27.
High pharmacokinetic variability of voriconazole is mainly explained by CYP2C19 phenotype, but there are still unknown factors affecting the variability. In this study, the effect of solute carrier organic anion transporter family member 2B1 (SLCO2B1) genotype on the pharmacokinetics (PKs) of voriconazole was evaluated in 12 healthy CYP2C19 poor metabolizers after a single administration of voriconazole 200 mg intravenously and orally. In addition, the influence of CYP3A4 enzyme activity was also explored. The oral absorption of voriconazole was decreased and delayed in the subjects with the SLCO2B1 c.*396T>C variant compared to the subjects with wild type. However, the CYP3A activity markers measured in this study did not show significant association with metabolism of voriconazole. The results suggest that the SLCO2B1 c.*396T>C may be associated with the decreased function of intestinal OATP2B1, and it could contribute to interindividual PK variability of voriconazole.
伏立康唑的药代动力学变异性较高，主要与 CYP2C19 表型有关，但仍存在影响变异的未知因素。在这项研究中，12 名健康的 CYP2C19 弱代谢者在单次静脉和口服伏立康唑 200mg 后，评估了溶质载体有机阴离子转运家族成员 2B1（SLCO2B1）基因型对伏立康唑药代动力学（PKs）的影响。此外，还探讨了 CYP3A4 酶活性的影响。与野生型相比，SLCO2B1 c.*396T>C 变异的受试者的伏立康唑口服吸收减少且延迟。然而，本研究中测量的 CYP3A 活性标志物与伏立康唑的代谢没有显著关联。结果表明，SLCO2B1 c.*396T>C 可能与肠 OATP2B1 功能降低有关，可能导致伏立康唑个体间 PK 变异性。
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