Lower than expected maraviroc concentrations in cerebrospinal fluid exceed the wild-type CC chemokine receptor 5-tropic HIV-1 50% inhibitory concentration.

TitleLower than expected maraviroc concentrations in cerebrospinal fluid exceed the wild-type CC chemokine receptor 5-tropic HIV-1 50% inhibitory concentration.
Publication TypeJournal Article
Year of Publication2012
AuthorsCroteau, D, Best, BM, Letendre, S, Rossi, SS, Ellis, RJ, Clifford, DB, Collier, AC, Gelman, BB, McArthur, JC, McCutchan, JAllen, Morgello, S, Grant, I
Corporate AuthorsCHARTER Group
JournalAIDS
Volume26
Issue7
Pagination890-3
Date Published2012 Apr 24
ISSN1473-5571
KeywordsAdult, CCR5 Receptor Antagonists, CHARTER, Chromatography, Reverse-Phase, Cross-Sectional Studies, Cyclohexanes, Female, HIV Infections, HIV-1, Humans, Inhibitory Concentration 50, Internal, Male, Maraviroc, Middle Aged, RNA, Viral, Tandem Mass Spectrometry, Triazoles
Abstract

To measure maraviroc total cerebrospinal fluid (CSF) concentrations and compare them with total and unbound plasma concentrations. Total maraviroc was measured by reverse-phase high-performance liquid chromatography with tandem mass spectrometry, whereas ultrafiltration was used for unbound maraviroc. Maraviroc was detected in all nine CSF/plasma pairs with a median CSF total concentration of 2.4 ng/ml. CSF concentrations exceeded the 50% inhibitory concentration of wild-type CC chemokine receptor 5-tropic HIV-1 in all specimens. CSF concentrations are lower than expected based on plasma concentrations and physicochemical characteristics. Unbound maraviroc plasma concentrations may be informative in estimating concentrations in CSF.

DOI10.1097/QAD.0b013e328351f627
Alternate JournalAIDS
PubMed ID22313954
PubMed Central IDPMC3454507
Grant ListN01 MH022005 / MH / NIMH NIH HHS / United States
N01MH22005 / MH / NIMH NIH HHS / United States
U01 MH083506 / MH / NIMH NIH HHS / United States
U01 MH83506 / MH / NIMH NIH HHS / United States