Physiologically Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long-Acting Nanoformulations for HIV

Rajith K.R. Rajoli, David J. Back, Steve Rannard, Caren L. Freel Meyers, Charles Flexner, Andrew Owen, Marco Siccardi

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives: Antiretrovirals are currently used for the treatment and prevention of HIV infection. However, poor adherence and low tolerability of some existing oral formulations can hinder their efficacy. Long-acting (LA) injectable nanoformulations could help address these complications by simplifying antiretroviral administration. The aim of this study is to inform the optimisation of intramuscular LA formulations for eight antiretrovirals through physiologically based pharmacokinetic (PBPK) modelling. Methods: A whole-body PBPK model was constructed using mathematical descriptions of molecular, physiological and anatomical processes defining pharmacokinetics. These models were validated against available clinical data and subsequently used to predict the pharmacokinetics of injectable LA formulations Results: The predictions suggest that monthly intramuscular injections are possible for dolutegravir, efavirenz, emtricitabine, raltegravir, rilpivirine and tenofovir provided that technological challenges to control their release rate can be addressed. Conclusions: These data may help inform the target product profiles for LA antiretroviral reformulation strategies.

Original languageEnglish (US)
Pages (from-to)639-650
Number of pages12
JournalClinical Pharmacokinetics
Volume54
Issue number6
DOIs
StatePublished - Dec 19 2015

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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