H A Elmekawy1, F Belal2, A E Abdelaziz3, K S Abdelkawy1, A A Ali1, F Elbarbry4. 1. Department of Clinical Pharmacy, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh, 33511, Egypt. 2. Department of Analytical Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt. 3. Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh, Egypt. 4. Pacific University Oregon School of Pharmacy, Hillsboro, OR, 97123, USA. Fawzy.elbarbry@pacificu.edu.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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 (AUC0-∞) and maximum plasma concentration (Cmax) of atorvastatin by 65.5% and 156.0%, respectively. Also, atorvastatin caused a significant increase in the AUC0-∞ and Cmax of sofosbuvir by 32.0% and 11.0%, respectively. Similarly, AUC0-∞ and Cmax of sofosbuvir metabolite significantly increased by 84.0% and 74.0%, respectively. However, ledipasvir AUC0-∞ showed no significant change after atorvastatin intake. The elimination rate in all drugs revealed no significant changes. CONCLUSION: After concurrent administration of FDCSL with atorvastatin, the AUC0-∞ 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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 (AUC0-∞) and maximum plasma concentration (Cmax) of atorvastatin by 65.5% and 156.0%, respectively. Also, atorvastatin caused a significant increase in the AUC0-∞ and Cmax of sofosbuvir by 32.0% and 11.0%, respectively. Similarly, AUC0-∞ and Cmax of sofosbuvir metabolite significantly increased by 84.0% and 74.0%, respectively. However, ledipasvir AUC0-∞ showed no significant change after atorvastatin intake. The elimination rate in all drugs revealed no significant changes. CONCLUSION: After concurrent administration of FDCSL with atorvastatin, the AUC0-∞ 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.
Authors: Eric Lawitz; Fred F Poordad; Phillip S Pang; Robert H Hyland; Xiao Ding; Hongmei Mo; William T Symonds; John G McHutchison; Fernando E Membreno Journal: Lancet Date: 2013-11-05 Impact factor: 79.321
Authors: Ahmed Elgharably; Asmaa I Gomaa; Mary Me Crossey; Peter J Norsworthy; Imam Waked; Simon D Taylor-Robinson Journal: Int J Gen Med Date: 2016-12-20
Authors: Ossama A Ahmed; Hany H Kaisar; Rehab Badawi; Nehad Hawash; Hossam Samir; Sherif St Shabana; Mohamed Hassan A Fouad; Fatma H Rizk; Samy A Khodeir; Sherief Abd-Elsalam Journal: Infect Drug Resist Date: 2018-03-01 Impact factor: 4.003
Authors: Nezam Afdhal; K Rajender Reddy; David R Nelson; Eric Lawitz; Stuart C Gordon; Eugene Schiff; Ronald Nahass; Reem Ghalib; Norman Gitlin; Robert Herring; Jacob Lalezari; Ziad H Younes; Paul J Pockros; Adrian M Di Bisceglie; Sanjeev Arora; G Mani Subramanian; Yanni Zhu; Hadas Dvory-Sobol; Jenny C Yang; Phillip S Pang; William T Symonds; John G McHutchison; Andrew J Muir; Mark Sulkowski; Paul Kwo Journal: N Engl J Med Date: 2014-04-11 Impact factor: 91.245