Pharmacokinetics of a long-acting nanoformulated dolutegravir prodrug in rhesus macaques

JoEllyn M McMillan, Adam Szlachetka, Lara Slack, Brady Sillman, Benjamin Lamberty, Brenda Morsey, Shannon Callen, Nagsen Gautam, Yazen Alnouti, Benson J Edagwa, Howard Eliot Gendelman, Howard S Fox

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere01316-17
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number1
DOIs
StatePublished - Jan 1 2018

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Prodrugs
Macaca mulatta
Pharmacokinetics
Intramuscular Injections
Half-Life
Body Weight
Pharmaceutical Preparations
dolutegravir

Keywords

  • Dolutegravir
  • Long-acting antiretrovirals
  • Monkeys
  • Nanoformulated antiretrovirals

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Pharmacokinetics of a long-acting nanoformulated dolutegravir prodrug in rhesus macaques. / McMillan, JoEllyn M; Szlachetka, Adam; Slack, Lara; Sillman, Brady; Lamberty, Benjamin; Morsey, Brenda; Callen, Shannon; Gautam, Nagsen; Alnouti, Yazen; Edagwa, Benson J; Gendelman, Howard Eliot; Fox, Howard S.

In: Antimicrobial Agents and Chemotherapy, Vol. 62, No. 1, e01316-17, 01.01.2018.

Research output: Contribution to journalArticle

McMillan, JoEllyn M ; Szlachetka, Adam ; Slack, Lara ; Sillman, Brady ; Lamberty, Benjamin ; Morsey, Brenda ; Callen, Shannon ; Gautam, Nagsen ; Alnouti, Yazen ; Edagwa, Benson J ; Gendelman, Howard Eliot ; Fox, Howard S. / Pharmacokinetics of a long-acting nanoformulated dolutegravir prodrug in rhesus macaques. In: Antimicrobial Agents and Chemotherapy. 2018 ; Vol. 62, No. 1.
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AU - Callen, Shannon

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