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.
aDepartment of Neurosciences
bDepartment of Medicine
cDepartment of Pediatrics, Rady Children's Hospital
dDepartment of Psychiatry
eSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California
fWashington University, St Louis, Missouri
gUniversity of Washington, Seattle, Washington
hUniversity of Texas Medical Branch, Galveston, Texas
iJohns Hopkins University, Baltimore, Maryland
jMount Sinai School of Medicine, New York, New York, USA.
Correspondence to David Croteau, HIV Neurobehavioral Research Center, University of California San Diego, 220 Dickinson Street, Suite B, San Diego, CA 92103-8231, USA. Tel: +1 619 543 4755; fax: +1 619 543 1235; e-mail: email@example.com
Received 22 December, 2011
Revised 20 January, 2012
Accepted 30 January, 2012
The results of this study were presented as a poster at the International Symposium on NeuroVirology (ISNV); 12–16 October 2010; Milan, Italy.