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Updated: May 15, 2026
08:23
Quantitative Measurement of Intrathecally Synthesized Proteins in Mice
Published on: November 29, 2019
Etravirine in CSF is highly protein bound
Anh Nguyen1, Steven Rossi, David Croteau
1Department of Pediatrics (Rady Children's Hospital), University of California San Diego, 3020 Childrens Way, San Diego, CA 92123, USA.
The Journal of Antimicrobial Chemotherapy
|January 22, 2013
Summary
Unbound etravirine concentrations in cerebrospinal fluid (CSF) did not reach levels needed to inhibit wild-type HIV, suggesting potential challenges in treating CNS infections. Further research is needed to optimize etravirine dosing for central nervous system (CNS) penetration.
Area of Science:
- Pharmacology
- Neuroscience
- Infectious Diseases
Background:
- Etravirine exhibits high protein binding, limiting its unbound fraction available for central nervous system (CNS) penetration.
- Understanding etravirine's CNS pharmacokinetics is crucial for evaluating its efficacy against HIV in the brain.
Purpose of the Study:
- To compare total and unbound etravirine concentrations in cerebrospinal fluid (CSF) and plasma.
- To assess etravirine CSF concentrations against the in vitro median inhibitory concentration (IC50) for wild-type HIV.
Main Methods:
- Measurement of total and bound etravirine in 17 CSF and plasma pairs using liquid chromatography-tandem mass spectrometry and radioligand displacement.
- Calculation of unbound etravirine concentrations from bound fractions.
- Assay dynamic range: 7.8–2000 ng/mL (plasma) and 0.78–200 ng/mL (CSF).
Main Results:
- Median unbound etravirine concentration in CSF was 0.13 ng/mL.
- Etravirine demonstrated high protein binding in both plasma (96%) and CSF (98.4%).
- CSF unbound etravirine concentrations remained below the wild-type HIV IC50 (0.9 ng/mL) in all subjects.
Conclusions:
- Unbound etravirine concentrations in the CNS may be insufficient to effectively inhibit HIV replication.
- Etravirine's high protein binding significantly impacts its CNS penetration and potential therapeutic efficacy for neurological HIV infections.
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