Keywords
DHBV; Lamivudine; Pharmacokinetics; Pharmacodynamics; HBV; Pekin Ducks
Abstract
Purpose: The Duck Hepatitis B Virus (DHBV)-infected Pekin duck model has been shown to be a reference model for the evaluation of anti-HBV treatments. The purpose of the current study was to characterize the pharmacokinetic and pharmacodynamic profiles of lamivudine, a potent nucleoside inhibitor of HBV replication, in DHBV-infected Pekin ducks.
Methods: Lamivudine serum concentrations were measured by LC-ESI-MS/MS following the administration of 80mg/kg IV, 200 mg/kg IM and 480 mg/kg PO of lamivudine to DHBV-infected Pekin ducks. Whereas, DHBV viremia levels were measured by real-time-PCR before, during and after 6-week lamivudine treatment of 40mg/ kg IM daily, or 100 or 200 mg/kg PO daily.
Results: The average apparent total body clearance and volume of distribution of lamivudine were 0.29 L/ hr/kgand0.65 L/kg, respectively. The average area under the concentration-time curve was 318, 661 and 1344 µg.hr/mL for 80mg/kg IV, 200 mg/kg IM and 480 mg/kg PO of lamivudine, respectively. 6-week lamivudine treatment of 100 mg/kg and 200 mg/kg PO were indifferently able to significantly lower DHBV titers compared with control and 40 mg/kg IM groups. However, the latent suppression of DHBV titers after the termination of lamivudine treatment was significantly more in 200 mg/kg PO compared with 100 mg/kg PO.
Conclusions: Our results suggest that the optimum dose of lamivudine against chronic HBV is higher than the current recommended dose in human.
Citation
Anwar-Mohamed A, El-Sherbeni AA, Poirier L, Fakheri M, Fakheri A, Johnson J, Hockman D, et al. Determination of Pharmacokinetics and Pharmacodynamics of Lamivudine After Highdoses in Duck Hepatitis B Virus-Infected Pekin Ducks. SM J Hepat Res Treat. 2017; 3(1): 1015. https://dx.doi.org/10.36876/smjhrt.1015