Translational pharmacokinetic-pharmacodynamic modelling; application to cardiovascular safety data for PF-00821385, a novel HIV agent.

Aim: To assess the translation of pharmacokinetic-pharmacodynamic (PK-PD) relationships for heart rate effects of PF-00821385 in dog and man.

Methods: Cardiovascular telemetric parameters and concentration data were available for animals receiving active doses (0.5-120 mg kg(-1), n= 4) or vehicle.

Pharmacokinetic-pharmacodynamic modeling of alpha interferon response induced by a Toll-like 7 receptor agonist in mice.

Recombinant alpha interferon (IFN-alpha) is used in the treatment of hepatitis C virus (HCV)-infected patients but is not optimal in terms of efficacy or tolerability. Toll-like 7 receptor (TLR-7) agonists stimulate the innate immune system to produce, among other cytokines, IFN-alpha and are being evaluated as alternative drugs to treat HCV infection. This paper describes the application of pharmacokinetic-pharmacodynamic (PK-PD) modeling to understanding the behavior of a TLR-7 agonist [9-benzyl-8-hydroxy-2-(2-methoxyethoxy) adenine (BHMA)] in mice, using IFN-alpha as a biomarker.