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

AIDS. 2012 Apr 24;26(7):890-3. doi: 10.1097/QAD.0b013e328351f627.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • CCR5 Receptor Antagonists
  • Chromatography, Reverse-Phase
  • Cross-Sectional Studies
  • Cyclohexanes / blood
  • Cyclohexanes / cerebrospinal fluid*
  • Cyclohexanes / therapeutic use
  • Female
  • HIV Infections / blood
  • HIV Infections / cerebrospinal fluid*
  • HIV Infections / drug therapy
  • HIV-1*
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Maraviroc
  • Middle Aged
  • RNA, Viral / blood
  • Tandem Mass Spectrometry
  • Triazoles / blood
  • Triazoles / cerebrospinal fluid*
  • Triazoles / therapeutic use

Substances

  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • RNA, Viral
  • Triazoles
  • Maraviroc