Karolien Dams*, Philippe G Jorens, Jonas Weyler, Sven Francque, Thomas Vanwolleghem, David M Burger
Background and objectives: Tenofovir disoproxil fumarate (TDF) is a prodrug of the acyclic nucleotide reverse transcriptase inhibitor tenofovir which is indicated for use in the treatment of chronic hepatitis B virus infection. Elimination of tenofovir happens primarily by the kidneys. The aim of this study was to evaluate the pharmacokinetics of tenofovir in a subject with severe renal impairment, undergoing different modalities of renal replacement therapy, first continuous veno-venous hemofiltration (CVVH) followed by intermittent hemodialysis (IHD) and ultrafiltration (UF) only, in order to provide dosing guidance for this specific patient population.
Study design: Serial serum samples were collected pre-dose and up to 72 h post-dosing TDF during CVVH, IHD and a UF session. Serum tenofovir concentrations in serum were analyzed using a validated LC-MS/MS technique.
Results: Tenofovir serum levels during CVVH were well above the accepted therapeutic window of 0.05-0.30 mg/L. The peak concentrations were higher and it took up to 44 hours to bring the levels down to the therapeutic window. As expected, the clearance of tenofovir was slower on IHD and absent during UF.
Conclusion: Tenofovir disoproxil fumarate 245 mg every four days in subjects on CVVH targets an adequate tenofovir exposure and can be adopted as an appropriate dosing interval. Our data demonstrate the adequacy of a once-weekly dose during IHD sessions and the absence of clearance during ultrafiltration. Both observations are helpful in guiding patients on first-line antiviral drug treatment for chronic HBV infection.
Published Date: 2020-01-16; Received Date: 2020-01-03