Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Neurosciences and Behavioural Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Br J Clin Pharmacol. 2021 Oct;87(10):4013-4019. doi: 10.1111/bcp.14829. Epub 2021 Apr 12.
Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating cytochrome P450 protein (CYP) activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV.
Patients with HCV infection (n = 23) at different fibrosis stages were allocated into groups 1 (F0/F1 and F2, mild to moderate fibrosis) and 2 (F3 and F4, advanced fibrosis stages). Phase 1 was conducted before the treatment with direct-acting antivirals (DAAs) and phase 2 after the sustained virological response. Participants were administered 2 mg of a single oral dose of omeprazole (OME) as probe drug in both phases. Metabolic ratios (MRs) (plasma samples collected at 4 h after OME administration) were calculated by dividing plasma concentrations of 5-hydroxyomeprazole by OME.
The MRs for group 1 were 0.45 (0.34-0.60, 90% confidence interval) and 0.69 (0.50-0.96) for phases 1 and 2, respectively, while the MRs for group 2 were 0.25 (0.21-0.31) and 0.41 (0.30-0.56) for phases 1 and 2, respectively. MRs were different (P < .05) between phases 1 and 2 for both groups, as well as between groups 1 and 2 in phase 1, but not in phase 2 (P > .05).
Both groups presented different MRs before and after treatment with DAAs, evidencing that CYP2C19 inhibition during inflammation was at least partially reversed after DAA treatment. Groups 1 and 2 were also found to be different in phase 1 but not phase 2, showing that CYP2C19 metabolic activity does not differ between groups after DAA treatment.
丙型肝炎病毒（HCV）感染会引发炎症反应，从而选择性地调节细胞色素 P450 蛋白（CYP）的活性。本研究评估了慢性 HCV 对 HCV 患者 CYP2C19 活性的影响。
将不同纤维化阶段的 HCV 感染患者（n=23）分为两组：1 组（F0/F1 和 F2，轻度至中度纤维化）和 2 组（F3 和 F4，晚期纤维化阶段）。第 1 阶段在接受直接作用抗病毒药物（DAA）治疗之前进行，第 2 阶段在持续病毒学应答之后进行。在两个阶段中，参与者均给予 2mg 单次口服剂量的奥美拉唑（OME）作为探针药物。代谢比（MRs）（在 OME 给药后 4 小时采集的血浆样本）通过将 5-羟奥美拉唑的血浆浓度除以 OME 来计算。
第 1 阶段，1 组的 MRs 分别为 0.45（0.34-0.60，90%置信区间）和 0.69（0.50-0.96），第 2 阶段的 MRs 分别为 0.25（0.21-0.31）和 0.41（0.30-0.56）。两组在第 1 阶段和第 2 阶段的 MRs 均不同（P<.05），1 组和 2 组在第 1 阶段的 MRs 也不同，但在第 2 阶段（P>.05）则无差异。
两组在接受 DAA 治疗前后均表现出不同的 MRs，表明 CYP2C19 抑制在炎症期间至少部分在 DAA 治疗后得到逆转。第 1 阶段的 1 组和 2 组也存在差异，但第 2 阶段则无差异，表明 DAA 治疗后两组之间的 CYP2C19 代谢活性没有差异。
