Trial reportEuropean journal of clinical pharmacology2008
CYP3A induction and inhibition by different antiretroviral regimens reflected by changes in plasma 4beta-hydroxycholesterol levels.
Trial report in European journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01105611 (An Open-label, Randomised Pilot Study Comparing the Efficacy, Safety and Tolerability of Raltegravir With Protease Inhibitor-based Therapy in Treatment-naïve, HIV/Hepatitis C Co-infected Injecting Drug Users Receiving Methadone), which is not on this map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
An Open-label, Randomised Pilot Study Comparing the Efficacy, Safety and Tolerability of Raltegravir With Protease Inhibitor-based Therapy in Treatment-naïve, HIV/Hepatitis C Co-infected Injecting Drug Users Receiving Methadone
Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- Pharmacokinetics of Ruxolitinib in HIV Suppressed Individuals on Antiretroviral Agent Therapy from the ACTG A5336 Study.Journal of clinical pharmacology · 2021Trial
- Effect of Antiretroviral Therapy on Plasma Concentrations of Chloroquine and Desethyl-chloroquine.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
- Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014Trial
- Induction of CYP2C19 and CYP3A activity following repeated administration of efavirenz in healthy volunteers.Clinical pharmacology and therapeutics · 2012Trial
- Impact of efavirenz on intestinal metabolism and transport: insights from an interaction study with ezetimibe in healthy volunteers.Clinical pharmacology and therapeutics · 2012Trial
- Application of Virtual Twin PBPK Models in Individuals with Obesity via CYP3A4 Phenotyping Using Endogenous Biomarker Data.Clinical pharmacology and therapeutics · 2026Article
- Impact of Efavirenz on Heme Protein Induction and Biomarkers: Insights From In Vitro Experiments and a Clinical Study.Clinical and translational science · 2026Article
- 1β-Hydroxydeoxycholic acid as an endogenous biomarker in human plasma for assessment of drug-drug interaction with moderate CYP3A inhibitor.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework.Pharmaceutics · 2024Article
- Investigation of pharmacokinetic drug interaction between clesacostat and DGAT2 inhibitor ervogastat in healthy adult participants.Clinical and translational science · 2024Article
- Investigation of CYP3A induction by PF-05251749 in early clinical development: comparison of linear slope physiologically based pharmacokinetic prediction and biomarker response.Clinical and translational science · 2022Article
- Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.European journal of clinical pharmacology · 2022Article
- The Effect of Modafinil on the Safety and Pharmacokinetics of Lorlatinib: A Phase I Study in Healthy Participants.Clinical pharmacokinetics · 2021Article
- Assessment of Vedolizumab Disease-Drug-Drug Interaction Potential in Patients With Inflammatory Bowel Diseases.Clinical pharmacology in drug development · 2021Review
- Structural Perspectives of the CYP3A Family and Their Small Molecule Modulators in Drug Metabolism.Liver research (Beijing, China) · 2019Article
- Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment.Clinical pharmacology : advances and applications · 2019Article
- Gjestad et al. reply to 'Was 4β-hydroxycholesterol ever going to be a useful marker of CYP3A4 activity?' by Neuhoff and Tucker.British journal of clinical pharmacology · 2018Article
- 4β-Hydroxycholesterol level significantly correlates with steady-state serum concentration of the CYP3A4 substrate quetiapine in psychiatric patients.British journal of clinical pharmacology · 2017Article
- Impact of genetic and nongenetic factors on interindividual variability in 4β-hydroxycholesterol concentration.European journal of clinical pharmacology · 2017Article
- 4β-Hydroxycholesterol Level in Patients With Rheumatoid Arthritis Before vs. After Initiation of bDMARDs and Correlation With Inflammatory State.Clinical and translational science · 2017Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
OBJECTIVE AND
methodsA member of the major human cytochrome P450 superfamily of hemoproteins, CYP3A4/5, converts cholesterol into 4beta-hydroxycholesterol. We studied plasma 4beta-hydroxycholesterol levels prior to and 4 weeks after initiating antiretroviral therapy that included efavirenz, ritonavir-boosted atazanavir or ritonavir-boosted lopinavir with the aim of exploring the usefulness of plasma 4beta-hydroxycholesterol levels as an endogenous biomarker of CYP3A activity. Efavirenz is an inducer of CYP3A, whereas the ritonavir-boosted regimens are net inhibitors of CYP3A.
resultsIn patients treated with efavirenz, the median plasma 4beta-hydroxycholesterol level increased by 46 ng/mL (p = 0.004; n = 11). In contrast, patients given ritonavir-boosted atazanavir showed a median decrease in plasma 4beta-hydroxycholesterol of -9.4 ng/mL (p = 0.0003; n = 22), and those given ritonavir-boosted lopinavir showed a median change from baseline of -5.8 ng/mL (p = 0.38; n = 19). There were significant between-group differences in the effects of antiretroviral treatment on plasma 4beta-hydroxycholesterol levels (p < 0.0001).
conclusionChanges in plasma 4beta-hydroxycholesterol following the initiation of efavirenz- or atazanavir/ritonavir-based antiretroviral therapy reflected the respective net increase and decrease of CYP3A activity of these regimens. The plasma 4beta-hydroxycholesterol level did not indicate a net CYP3A inhibition in the lopinavir/ritonavir arm, possibly because of concomitant enzyme induction.
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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.