Merck & Co., Inc., Kenilworth, NJ, USA.
Eur J Clin Pharmacol. 2019 May;75(5):665-675. doi: 10.1007/s00228-018-2585-3. Epub 2019 Jan 25.
To describe the phase 1 and population pharmacokinetic investigations that support dosing recommendations for elbasvir/grazoprevir (EBR/GZR) in hepatitis C virus-infected people with advanced chronic kidney disease.
This was an open-label, two-part, multiple-dose trial (MK-5172 PN050; NCT01937975) in 24 non-HCV-infected participants with end-stage renal disease (ESRD) or severe renal impairment who received once-daily EBR 50 mg and GZR 100 mg for 10 days. Population pharmacokinetic analyses from the phase 3 C-SURFER study (PN052, NCT02092350) were also conducted.
When comparing haemodialysis (HD) and non-HD days in participants with ESRD, geometric mean ratios (GMRs) (90% confidence intervals [CIs]) for EBR and GZR AUC were 1.14 (1.08-1.21) and 0.97 (0.87-1.09). When comparing ESRD and healthy participants, GMRs (90% CIs) for EBR and GZR AUC were 0.99 (0.75-1.30) and 0.83 (0.56-1.22) on HD days, and 0.86 (0.65-1.14) and 0.85 (0.58-1.25) on non-HD days. GMRs (90% CIs) for AUC in participants with severe renal impairment relative to healthy controls were 1.65 (1.09-2.49) for GZR and 1.86 (1.38-2.51) for EBR. In population modelling of data from C-SURFER, absolute geometric means of steady-state EBR AUC were 2.78 and 3.07 μMh (HD and non-HD recipients) and GZR AUC were 1.80 and 2.34 μMh (HD and non-HD recipients).
EBR/GZR represents an important treatment option for HCV infection in people with severe renal impairment and those with ESRD. No dosage adjustment of EBR/GZR is required in people with any degree of renal impairment, including those receiving dialysis.
描述支持在患有慢性肾脏病（CKD）终末期或严重肾功能损害的丙型肝炎病毒（HCV）感染者中给予 Elbasvir/Grazoprevir（EBR/GZR）剂量建议的 1 期和群体药代动力学研究。
这是一项在 24 名非 HCV 感染的终末期肾病（ESRD）或严重肾功能损害患者中进行的开放性、两部分、多次给药试验（MK-5172 PN050；NCT01937975），患者每天接受一次 EBR 50 mg 和 GZR 100 mg，持续 10 天。还对来自 3 期 C-SURFER 研究（PN052，NCT02092350）的群体药代动力学分析进行了研究。
在 ESRD 患者中比较血液透析（HD）和非 HD 天，EBR 和 GZR AUC 的几何均数比值（GMR）（90%置信区间[CI]）分别为 1.14（1.08-1.21）和 0.97（0.87-1.09）。当比较 ESRD 和健康参与者时，EBR 和 GZR AUC 的 GMR（90%CI）在 HD 天分别为 0.99（0.75-1.30）和 0.83（0.56-1.22），在非 HD 天分别为 0.86（0.65-1.14）和 0.85（0.58-1.25）。与健康对照者相比，严重肾功能损害患者的 GZR 和 EBR AUC 的 GMR（90%CI）分别为 1.65（1.09-2.49）和 1.86（1.38-2.51）。在 C-SURFER 数据的群体模型中，稳态 EBR AUC 的绝对几何均值分别为 2.78 和 3.07 μMh（HD 和非 HD 接受者）和 GZR AUC 分别为 1.80 和 2.34 μMh（HD 和非 HD 接受者）。
EBR/GZR 是治疗严重肾功能损害和 ESRD 患者 HCV 感染的重要治疗选择。在任何程度的肾功能损害患者中，包括接受透析的患者，均无需调整 EBR/GZR 的剂量。
