Lower than expected maraviroc concentrations in cerebrospinal fluid exceed the wild-type CC chemokine receptor 5-tropic HIV-1 50% inhibitory concentration.
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.
Department of Neurosciences, Rady Children's Hospital, San Diego, California, USA. dcroteau@ucsd.edu
David
D
Croteau
Brookie M
BM
Best
Scott
S
Letendre
Steven S
SS
Rossi
Ronald J
RJ
Ellis
David B
DB
Clifford
Ann C
AC
Collier
Benjamin B
BB
Gelman
Justin C
JC
McArthur
John Allen
JA
McCutchan
Susan
S
Morgello
Igor
I
Grant
D000328:Adult; D065100:CCR5 Receptor Antagonists; D056148:Chromatography, Reverse-Phase; D003430:Cross-Sectional Studies; D003510:Cyclohexanes / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D053719:Tandem Mass Spectrometry; D014230:Triazoles / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use
D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D012367:RNA, Viral; D014230:Triazoles; D000077592:Maraviroc