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Therapeutic amprenavir concentrations in cerebrospinal fluid
David Croteau1, Scott Letendre, Brookie M Best
1Department of Neurosciences, University of California, San Diego, San Diego, California, USA. dcroteau@ucsd.edu
Antimicrobial Agents and Chemotherapy
|February 1, 2012
Summary
Fosamprenavir (FPV) effectively delivers amprenavir (APV) to the cerebrospinal fluid (CSF), exceeding therapeutic levels for HIV control. This antiretroviral therapy supports central nervous system (CNS) HIV management.
Area of Science:
- Pharmacokinetics
- Neurovirology
- HIV/AIDS Research
Background:
- Higher cerebrospinal fluid (CSF) antiretroviral concentrations correlate with better HIV control in the CNS.
- Neurocognitive outcomes may improve with enhanced CSF drug penetration.
Purpose of the Study:
- To evaluate amprenavir (APV) concentrations in CSF following fosamprenavir (FPV) administration.
- To determine if APV levels in CSF are within the therapeutic range for HIV treatment.
Main Methods:
- Analysis of 119 matched CSF-plasma samples from 75 subjects on FPV-containing regimens.
- Quantification of total APV using HPLC (plasma) and LC/MS/MS (CSF).
- Comparison of CSF APV concentrations to the 50% inhibitory concentration (IC₅₀) for wild-type HIV.
Main Results:
- APV was detected in over 97% of CSF specimens.
- Median CSF APV concentration was 24.8 ng/ml, exceeding the HIV IC₅₀ by 4.4-fold.
- CSF APV levels correlated significantly with plasma concentrations and sampling intervals.
Conclusions:
- Fosamprenavir administration results in therapeutic concentrations of amprenavir in the CSF.
- FPV contributes to controlling HIV replication within the central nervous system (CNS).
- FPV is a valuable component of antiretroviral regimens for CNS HIV management.
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