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

Croteau, Davida; Best, Brookie M.c,e; Letendre, Scottb; Rossi, Steven S.c; Ellis, Ronald J.a; Clifford, David B.f; Collier, Ann C.g; Gelman, Benjamin B.h; Mcarthur, Justin C.i; McCutchan, John Allenb; Morgello, Susanj; Grant, Igord; for the CHARTER Group

AIDS:
doi: 10.1097/QAD.0b013e328351f627
Research Letters
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.

Author Information

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: dcroteau@ucsd.edu

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.

© 2012 Lippincott Williams & Wilkins, Inc.