Department of Clinical Pharmacy, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh, 33511, Egypt.
Department of Analytical Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt.
Eur J Clin Pharmacol. 2021 Sep;77(9):1369-1379. doi: 10.1007/s00228-021-03130-z. Epub 2021 Apr 1.
Comorbid conditions of heart and liver disorders added to HCV-induced hepatic steatosis make co-administration of statins, and direct-acting antivirals is common in clinical practice. This study aimed to evaluate the pharmacokinetic interaction of atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir "FDCSL" with rationalization to the underlying mechanism.
A randomized, three-phase crossover study that involves 12 healthy volunteers was performed. Participants received a single-dose of atorvastatin 80 mg alone, atorvastatin 80-mg plus tablets containing 400/90 mg FDCSL, or tablets containing 400/90 mg FDCSL alone. Plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for atorvastatin, sofosbuvir, ledipasvir, and sofosbuvir metabolite "GS-331007," and their pharmacokinetics parameters were determined.
Compared to atorvastatin alone, the administration of FDCSL caused a significant increase in both areas under the concentration-time curve from time zero to infinity (AUC) and maximum plasma concentration (C) of atorvastatin by 65.5% and 156.0%, respectively. Also, atorvastatin caused a significant increase in the AUC and C of sofosbuvir by 32.0% and 11.0%, respectively. Similarly, AUC and C of sofosbuvir metabolite significantly increased by 84.0% and 74.0%, respectively. However, ledipasvir AUC showed no significant change after atorvastatin intake. The elimination rate in all drugs revealed no significant changes.
After concurrent administration of FDCSL with atorvastatin, the AUC of both atorvastatin and sofosbuvir were increased. Caution should be taken with close monitoring for possible side effects after co-administration of atorvastatin and FDCSL in clinical practice.
心脏和肝脏疾病的合并症增加了 HCV 引起的肝脂肪变性，因此他汀类药物和直接作用抗病毒药物的联合治疗在临床实践中很常见。本研究旨在评估阿托伐他汀与固定剂量复方索菲布韦/维帕他韦（FDCSL）联合用药的药代动力学相互作用，并对其潜在机制进行合理化分析。
本研究为一项随机、三交叉的临床试验，共纳入 12 名健康志愿者。参与者接受了阿托伐他汀 80mg 单剂量、阿托伐他汀 80mg 加含有 400/90mg FDCSL 的片剂或仅含有 400/90mg FDCSL 的片剂的单次给药。使用液相色谱-串联质谱法（LC-MS/MS）对阿托伐他汀、索非布韦、雷迪帕韦和索非布韦代谢物“GS-331007”的血浆样本进行分析，并确定其药代动力学参数。
与阿托伐他汀单药相比，FDCSL 给药使阿托伐他汀的 AUC 和 C 分别增加了 65.5%和 156.0%，同时使索非布韦的 AUC 和 C 分别增加了 32.0%和 11.0%。此外，索非布韦代谢物的 AUC 和 C 分别增加了 84.0%和 74.0%。然而，阿托伐他汀摄入后雷迪帕韦的 AUC 没有显著变化。所有药物的消除率均无显著变化。
在同时给予 FDCSL 和阿托伐他汀后，阿托伐他汀和索非布韦的 AUC 均增加。在临床实践中，当联合使用阿托伐他汀和 FDCSL 时，应密切监测可能出现的不良反应。
