Pharmacokinetics and pharmacodynamics modeling of lonafarnib in patients with chronic hepatitis delta virus infection.

ABSTRACT: The prenylation inhibitor lonafarnib (LNF) is a potent antiviral agent providing a breakthrough for the treatment of hepatitis delta virus (HDV). The current study used a maximum likelihood approach to model LNF pharmacokinetic (PK) and pharmacodynamic (PD) parameters and predict the dose needed to achieve 99% efficacy using data from 12 patients chronically infected with HDV and treated with LNF 100 mg twice daily (bid) (group 1) or 200 mg bid (group 2) for 28 days. The LNF-PK model predicted average steady-state LNF concentrations of 860 ng/mL and 1,734 ng/mL in groups 1 and 2, respectively, with an LNF absorption rate k_a = 0.43/hour and elimination rate k_e = 0.045/hour. The PK/PD model identified an average delay of 0.56 hours and an LNF concentration that decrease

SUBMITTER: Canini L 

PROVIDER: S-EPMC5721397 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature