Open AccessPharmacokinetic testing of a first-generation cabotegravir prodrug in rhesus macaques
Author(s) -
JoEllyn M McMillan,
Adam M. Szlachetka,
Tianhua Zhou,
Brenda Morsey,
B.G.H. Lamberty,
Shan Callen,
Nagsen Gautam,
Yazen Alnouti,
Benson Edagwa,
Howard Eliot Gendelman,
Howard S. Fox
Publication year - 2019
Publication title -
aids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.195
H-Index - 216
eISSN - 1473-5571
pISSN - 0269-9370
DOI - 10.1097/qad.0000000000002032
Subject(s) - prodrug , pharmacokinetics , poloxamer 407 , pharmacology , enfuvirtide , plasma chemistry , drug , medicine , plasma concentration , human immunodeficiency virus (hiv) , poloxamer , chemistry , virology , immunology , plasma , physics , organic chemistry , quantum mechanics , epitope , antigen , gp41 , copolymer , polymer
: 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.