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Pharmacokinetics of a CCR5 inhibitor in rhesus macaques following vaginal, rectal and oral application

Malcolm, R. K., Lowry, Deborah, Boyd, P., Geer, L., Veazey, R. S., Goldman, L., Klasse, P. J., Shattock, R. J. and Moore, J. P. (2014) Pharmacokinetics of a CCR5 inhibitor in rhesus macaques following vaginal, rectal and oral application. Journal of Antimicrobial Chemotherapy, 69 (5). pp. 1325-1329. [Journal article]

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URL: http://dx.doi.org/doi 10.1093/jac/dkt506

DOI: doi 10.1093/jac/dkt506


ObjectivesThis study measured and compared the pharmacokinetics of CMPD167, a small molecule antiretroviral CCR5 inhibitor with potential as an HIV microbicide, following vaginal, rectal and oral administration in rhesus macaques.MethodsA vaginal hydroxyethylcellulose (HEC) gel, a rectal HEC gel, a silicone elastomer matrix-type vaginal ring and an oral solution, each containing CMPD167, were prepared and administered to rhesus macaques pretreated with Depo-Provera. CMPD167 concentrations in vaginal fluid, vaginal tissue (ring only), rectal fluid and blood plasma were quantified by HPLC–mass spectrometry.ResultsCMPD167 concentrations measured in rectal fluid, vaginal fluid and blood plasma were highly dependent on both the route of administration and the formulation type. Although rectal and vaginal fluid concentrations were highest when CMPD167 was administered locally (via either gel or ring), lower concentrations of the drug were also measured in these compartments following administration at the remote mucosal site or orally. CMPD167 levels in the vaginal and rectal fluid following oral administration were relatively low compared with local administration.ConclusionsThe study provides clear evidence for vaginal–rectal and rectal–vaginal drug transfer pathways and suggests that oral pre-exposure prophylaxis with CMPD167 may be less efficacious at preventing sexual transmission of HIV-1 than topically applied products.

Item Type:Journal article
Keywords:HIV microbicides, vaginal HEC gels, vaginal rings, rectal gels, pre-exposure prophylaxis, PrEP, CMPD167
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
ID Code:39116
Deposited By: Dr Deborah Lowry
Deposited On:02 Jan 2018 14:45
Last Modified:02 Jan 2018 14:45

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