Pharmacokinetic testing of a first-generation cabotegravir prodrug in rhesus macaques

Joellyn McMillan; Adam Szlachetka; Tian Zhou; Brenda Morsey; Benjamin Lamberty; Shannon Callen; Nagsen Gautam; Yazen Alnouti; Benson Edagwa; Howard E. Gendelman; Howard S. Fox

doi:10.1097/QAD.0000000000002032

Pharmacokinetic testing of a first-generation cabotegravir prodrug in rhesus macaques

Joellyn McMillan, Adam Szlachetka, Tian Zhou, Brenda Morsey, Benjamin Lamberty, Shannon Callen, Nagsen Gautam, Yazen Alnouti, Benson Edagwa, Howard E. Gendelman, Howard S. Fox

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Long-acting antiretrovirals can improve therapy and prevention for HIV-1 infection. Current long-acting cabotegravir (CAB LAP) can be administered every other month. Previously, we demonstrated that a myristoylated CAB prodrug encased in poloxamer 407 provided extended plasma drug concentrations. We now demonstrate that this first-generation nanoformulated prodrug can sustain plasma CAB concentrations above the protein-adjusted 90% inhibitory concentration for 4 months in rhesus macaques. A 2.5-fold extension in CAB half-life and a 1.6-fold increase in area under the concentration-time curve were observed compared with CAB LAP.

Original language	English (US)
Pages (from-to)	585-588
Number of pages	4
Journal	AIDS
Volume	33
Issue number	3
DOIs	https://doi.org/10.1097/QAD.0000000000002032
State	Published - Mar 1 2019

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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abstract = "Long-acting antiretrovirals can improve therapy and prevention for HIV-1 infection. Current long-acting cabotegravir (CAB LAP) can be administered every other month. Previously, we demonstrated that a myristoylated CAB prodrug encased in poloxamer 407 provided extended plasma drug concentrations. We now demonstrate that this first-generation nanoformulated prodrug can sustain plasma CAB concentrations above the protein-adjusted 90% inhibitory concentration for 4 months in rhesus macaques. A 2.5-fold extension in CAB half-life and a 1.6-fold increase in area under the concentration-time curve were observed compared with CAB LAP.",

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AU - McMillan, Joellyn

AU - Szlachetka, Adam

AU - Zhou, Tian

AU - Morsey, Brenda

AU - Lamberty, Benjamin

AU - Callen, Shannon

AU - Gautam, Nagsen

AU - Alnouti, Yazen

AU - Edagwa, Benson

AU - Gendelman, Howard E.

AU - Fox, Howard S.

PY - 2019/3/1

Y1 - 2019/3/1

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AB - Long-acting antiretrovirals can improve therapy and prevention for HIV-1 infection. Current long-acting cabotegravir (CAB LAP) can be administered every other month. Previously, we demonstrated that a myristoylated CAB prodrug encased in poloxamer 407 provided extended plasma drug concentrations. We now demonstrate that this first-generation nanoformulated prodrug can sustain plasma CAB concentrations above the protein-adjusted 90% inhibitory concentration for 4 months in rhesus macaques. A 2.5-fold extension in CAB half-life and a 1.6-fold increase in area under the concentration-time curve were observed compared with CAB LAP.

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Pharmacokinetic testing of a first-generation cabotegravir prodrug in rhesus macaques

Abstract

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