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

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

JoEllyn McMillan  1 , Adam Szlachetka  2   3 , Lara Slack  3 , Brady Sillman  2 , Benjamin Lamberty  2 , Brenda Morsey  2 , Shannon Callen  2 , Nagsen Gautam  4 , Yazen Alnouti  4 , Benson Edagwa  2 , Howard E Gendelman  1 , Howard S Fox  2
Affiliations

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

JoEllyn McMillan et al. Antimicrob Agents Chemother. .

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.

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Figures

FIG 1
FIG 1
White blood cell counts following NMDTG administration in rhesus macaques. Complete blood count (CBC) samples were collected into EDTA tubes and assessed by manual differentiation. Data are expressed as mean ± standard deviation (n = 3).
FIG 2
FIG 2
Plasma (A) and blood leukocyte (B) DTG and MDTG concentrations following NMDTG administration in rhesus macaques. Data are expressed as mean ± standard deviation (A, n = 3; B, n = 2 to 3). Dashed line indicates DTG PA-IC90 of 64 ng/ml.
See this image and copyright information in PMC

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