Physiologically Based Pharmacokinetic Models for the Optimization of Antiretroviral Therapy: Recent Progress and Future Perspective

Abstract

Anti-HIV therapy is characterized by the chronic administration of antiretrovirals (ARVs), and consequently, several problems can arise during the management of HIV-positive patients. ARV disposition can be simulated by combining system data describing a population of patients and in vitro drug data through physiologically based pharmacokinetic (PBPK) models, which mathematically describe absorption, distribution, metabolism and elimination. PBPK modeling can find application in the investigation of clinically relevant scenarios, while providing the opportunity for a better understanding of the mechanisms regulating drug distribution. In this review, we have analyzed the most recent applications of PBPK models for ARVs and highlighted some of the most interesting areas of use, such as drug–drug interaction, pharmacogenetics, factors regulating absorption and tissue penetration, as well as therapy optimization in special populations. The application of the PBPK modeling approach might not be limited to the investigation of hypothetical clinical issues, but could be used to inform future prospective clinical trials.

Keywords::

• antiretrovirals
• in vitro–in vivo extrapolation
• PBPK
• pharmacokinetics

Financial & competing interests disclosure

A Owen has received honoraria for lectures or advisory board meetings and/or research support research funding by Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Merck, Pfizer and Roche Pharmaceuticals. M Siccardi has received financial support from Simcyp Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

A Owen has received honoraria for lectures or advisory board meetings and/or research support research funding by Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Merck, Pfizer and Roche Pharmaceuticals. M Siccardi has received financial support from Simcyp Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.