In‐depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS‐331007 and ledipasvir in rat plasma using LC–MS. (23rd June 2022)

• Record Type: Journal Article
• Authors: Aboras, Sara I.; Korany, Mohamed A.; El‐Yazbi, Ahmed F.; Ragab, Marwa A. A.; Abdine, Heba H.
• Is Part Of: Biomedical chromatography. Volume 36:Number 9(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-23
• Subjects: LC–MS -- ledipasvir -- pharmacokinetics -- silymarin -- sofosbuvir; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.5427
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: The use of complementary medicine (CMD) for liver support in Hepatitis C virus (HCV) patients sometimes coincides with the administration of oral antiviral drugs to eradicate the virus. This calls for a deep investigation of CMD effects on the pharmacokinetic parameters of these drugs to ensure their safety and efficacy. Silymarin (SLY), as a CMD, was selected to be given orally to healthy male rats with sofosbuvir (SFB) and ledipasvir (LED), a common regimen in HCV treatment. A new and sensitive LC–MS method was validated for the bioassay of SLY, LED, SFB and its inactive metabolite, GS‐331007, in spiked plasma with lower limits of quantitation of 10, 1, 4 and 10 ng/ml, respectively. Moreover, the method was further applied to conduct a full pharmacokinetic profile of SFB, GS‐331007 and ledipasvir with and without SLY. It was found that co‐administration of SLY may expose the patient to unplanned high serum concentrations of SFB and LED. This could be accompanied by a decrease in SFB efficacy, potentially leading to therapeutic failure and the emergence of viral resistance.