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

McMillan, JoEllyna; Szlachetka, Adamb; Zhou, Tianc; Morsey, Brendaa; Lamberty, Benjamina; Callen, Shannona; Gautam, Nagsenc; Alnouti, Yazenc; Edagwa, Bensona; Gendelman, Howard E.a,c; Fox, Howard S.a

doi: 10.1097/QAD.0000000000002032
Research Letters

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.

aDepartment of Pharmacology and Experimental Neuroscience

bNebraska Nanomedicine Production Plant

cDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Correspondence to JoEllyn McMillan, PhD, and Howard E. Gendelman, MD, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800, USA. Tel: +1 402 559 3074; fax: +1 402 559 7495; e-mail:;

Received 2 August, 2018

Accepted 31 August, 2018

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