ArticleThe Journal of antimicrobial chemotherapy2013
Etravirine in CSF is highly protein bound.
Article in The Journal of antimicrobial chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Pharmacokinetics and antiviral activity of cabotegravir and rilpivirine in cerebrospinal fluid following long-acting injectable administration in HIV-infected adults.The Journal of antimicrobial chemotherapy · 2020Trial
- Antiretroviral drugs from multiple classes induce loss of excitatory synapses between hippocampal neurons in culture.Frontiers in pharmacology · 2024Article
- Drug Repositioning in Friedreich Ataxia.Frontiers in neuroscience · 2022Review
- Pharmacology of HIV Cure: Site of Action.Clinical pharmacology and therapeutics · 2021Review
- Pharmacologic approaches to HIV-associated neurocognitive disorders.Current opinion in pharmacology · 2020Review
- Clinical Pharmacokinetics and Pharmacodynamics of Etravirine: An Updated Review.Clinical pharmacokinetics · 2020Review
- Antiretroviral concentrations and surrogate measures of efficacy in the brain tissue and CSF of preclinical species.Xenobiotica; the fate of foreign compounds in biological systems · 2019Article
- An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.Bioorganic & medicinal chemistry · 2017Article
- Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain.Retrovirology · 2017Article
- Pharmacokinetic Properties of Anticancer Agents for the Treatment of Central Nervous System Tumors: Update of the Literature.Clinical pharmacokinetics · 2016Review
- Central nervous system penetration of antiretroviral drugs: pharmacokinetic, pharmacodynamic and pharmacogenomic considerations.Clinical pharmacokinetics · 2015Article
- Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.Clinical pharmacokinetics · 2014Review
- Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
objectivesEtravirine has high affinity for plasma drug-binding proteins, such as albumin and α1-acid glycoprotein, which limits the amount of unbound etravirine available to enter the CNS. The objective of this study was to compare total and unbound etravirine concentrations in CSF with plasma concentrations and the in vitro median inhibitory concentration (IC50) for wild-type HIV (0.9 ng/mL).
methodsTotal and bound etravirine concentrations were measured in 17 CSF and plasma pairs by isotope-dilution liquid chromatography tandem mass spectroscopy, radioligand displacement and ultracentrifugation. Unbound etravirine concentrations were calculated from the bound fraction. The dynamic range of the assay was 7.8-2000 (plasma) and 0.78-200 (CSF) ng/mL.
resultsSubjects were mostly middle-aged (median 43 years) white (78%) men (89%). All CSF etravirine concentrations were above the limit of quantification. Total and unbound median etravirine concentrations in CSF were 9.5 (IQR 6.4, 26.4) and 0.13 (IQR 0.08, 0.27) ng/mL, respectively. Etravirine was 96% (IQR 94.5, 97.2) protein bound in plasma and 98.4% (IQR 97.8, 98.8) in CSF. Total etravirine in CSF was 4.3% (IQR 3, 5.9) of total and 101% (IQR 76, 160) of unbound etravirine in plasma. There were no significant correlations between unbound etravirine concentrations and concentrations of albumin in plasma or CSF. Unbound etravirine concentrations in CSF did not reach the wild-type IC50 in any of the specimens.
conclusionsUnbound etravirine may not achieve optimal concentrations to inhibit HIV replication in the CNS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.