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

Clin Pharmacokinet. 2015 Jun;54(6):639-50. doi: 10.1007/s40262-014-0227-1.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Algorithms
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacokinetics*
  • Computer Simulation
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism*
  • Humans
  • Injections, Intramuscular
  • Intestinal Absorption
  • Male
  • Middle Aged
  • Models, Biological*
  • Nanomedicine / methods
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry
  • Young Adult


  • Anti-HIV Agents