Pharmacokinetics of a Long-Acting Nanoformulated Dolutegravir Prodrug in Rhesus Macaques

Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01316-17. doi: 10.1128/AAC.01316-17. Print 2018 Jan.

Abstract

A nanoformulated myristoylated dolutegravir prodrug (NMDTG) was prepared using good laboratory practice protocols. Intramuscular injection of NMDTG (118 ± 8 mg/ml, 25.5 mg of DTG equivalents/kg of body weight) to three rhesus macaques led to plasma DTG levels of 86 ± 12 and 28 ± 1 ng/ml on days 35 and 91, respectively. The NMDTG platform showed no significant adverse events. Further modification may further extend the drug's apparent half-life for human use.

Keywords: dolutegravir; long-acting antiretrovirals; monkeys; nanoformulated antiretrovirals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Delayed-Action Preparations
  • HIV Integrase Inhibitors / administration & dosage
  • HIV Integrase Inhibitors / blood
  • HIV Integrase Inhibitors / pharmacokinetics
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / blood
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics*
  • Injections, Intramuscular
  • Macaca mulatta
  • Male
  • Nanocomposites / administration & dosage
  • Oxazines
  • Piperazines
  • Prodrugs / administration & dosage
  • Prodrugs / chemical synthesis
  • Prodrugs / pharmacokinetics*
  • Pyridones

Substances

  • Delayed-Action Preparations
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Prodrugs
  • Pyridones
  • dolutegravir