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Abstract：
Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5-20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS-331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on- and off-dialysis studies. On the contrary, GS-331007 exhibited a 30% reduction in the area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24h) on dialysis days compared with non-dialysis days (AUC0-24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS-331007 was 9.35 (8.72-15.11) and 8.89 (8.52-14.07) mL/min, respectively. Subsequently, an alternate-day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen.
摘要：
Sofosbuvir/Velpatasvir（SOF/VEL）是用于慢性丙型肝炎（HCV）感染的组合药物。然而,关于SOF/VEL及其代谢物在血液透析患者中的药代动力学的信息有限。我们对12名泰国慢性HCV感染的血液透析患者进行了单剂量SOF/VEL（400/100mg）透析和不透析后的SOF/VEL的药代动力学参数进行了前瞻性研究，接受血液透析0.5-20年的患者。在给药前(0)和给药后0.5、1.0、2.0、2.5、3.0、3.5、4.0、5.0、6.0、8.0和12.0小时收集血样。还在给药前(0)和给药后1.0、2.0、3.0和4.0小时收集透析液样品。对血浆和透析液样品的SOF及其代谢物进行定量，GS-331007和VEL浓度使用完全验证的LCMS技术。此外,在所有患者中使用拟议的SOF/VEL减量方案进行了初步疗效研究.透析上和非透析研究之间的SOF/VELPK参数没有差异。相反,与非透析日相比，GS-331007在透析日从时间0到24h（AUC0-24h）的血浆浓度-时间曲线下面积减少了30％（AUC0-24h比率0.68vs.分别为1.04）。SOF和GS-331007的透析清除率分别为9.35(8.72-15.11)和8.89(8.52-14.07)mL/min,分别。随后，隔日给药SOF/VEL（400/100mg），持续12周，导致无法检测到的血浆HCV病毒载量无副作用。需要进一步的临床研究来验证我们建议的剂量减少方案的有效性和安全性。
