Pharmacokinetics of Daclatasvir, Sofosbuvir, and GS-331007 in a Prospective Cohort of Hepatitis C Virus–Positive Kidney Transplant Recipients

In this study, plasma samples of 16 HCV-positive kidney transplant recipients receiving daclatasvir and sofosbuvir were collected at 4 time points at days 1, 7, 14, 21, 56, and 84 after start of treatment. Inclusion criteria were stable graft function and an estimated glomerular filtration rate (eGFR)>30 mL/min/1.73 m2. Daclatasvir, sofosbuvir, and GS-331007 (inactive metabolite of sofosbuvir) plasma concentrations were determined using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Results: All patients showed a rapid virological response with HCV RNA below the detection limit 21 days after the start of therapy (medium time to viral clearance). No difference of the areas under the concentration–time curve (AUC) of daclatasvir, sofosbuvir, and GS-331007 was observed between patients with an eGFR below or ≥60 mL/min. For GS-331007, no relevant changes of trough levels were observed over time. Mean GS-331007 trough levels were 339.5 ± 174.9 ng/mL in patients with an eGFR ≥60 mL/min and 404.3 ± 226 ng/mL in patients with an eGFR
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research