Abstract | OBJECTIVES: Pharmacokinetic studies in animal models are important for assessing the prophylactic potential of antiretroviral drugs for HIV prevention. This study sought to identify clinically relevant doses of the marketed integrase inhibitors raltegravir, elvitegravir and dolutegravir in macaques and investigate drug penetration and antiviral activity in mucosal secretions. METHODS: RESULTS: CONCLUSIONS: We defined macaque doses of HIV integrase inhibitors that recapitulate human clinical doses, which will facilitate efficacy and dose escalation studies in macaques. High and sustained drug concentrations and activity in mucosal secretions suggest that integrase inhibitors are promising candidates for HIV prevention.
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Authors | Ivana Massud, Amy Martin, Chuong Dinh, James Mitchell, Leecresia Jenkins, Walid Heneine, Chou-Pong Pau, J Gerardo García-Lerma |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 70
Issue 5
Pg. 1473-81
(May 2015)
ISSN: 1460-2091 [Electronic] England |
PMID | 25630643
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US. |
Chemical References |
- Anti-HIV Agents
- Heterocyclic Compounds, 3-Ring
- Oxazines
- Piperazines
- Pyridones
- Quinolones
- Raltegravir Potassium
- elvitegravir
- dolutegravir
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Topics |
- Administration, Oral
- Animals
- Anti-HIV Agents
(administration & dosage, pharmacokinetics)
- Bodily Secretions
(chemistry)
- Chromatography, High Pressure Liquid
- Female
- Heterocyclic Compounds, 3-Ring
(administration & dosage, pharmacokinetics)
- Macaca mulatta
- Mucous Membrane
(chemistry)
- Oxazines
- Piperazines
- Plasma
(chemistry)
- Pyridones
- Quinolones
(administration & dosage, pharmacokinetics)
- Raltegravir Potassium
(administration & dosage, pharmacokinetics)
- Rectum
(chemistry)
- Tandem Mass Spectrometry
- Vagina
(chemistry)
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