Trial reportBritish journal of clinical pharmacology2014
Validation of 4β-hydroxycholesterol and evaluation of other endogenous biomarkers for the assessment of CYP3A activity in healthy subjects.
Trial report in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed.
- Serum 4β-hydroxycholesterol increases during fluconazole treatment.European journal of clinical pharmacology · 2021Trial
- Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Oral Venglustat in Healthy Volunteers.Clinical pharmacology in drug development · 2021Trial
- Safety and Pharmacokinetics of High-Dose TAS-303 in Healthy Japanese Volunteers: A Single-Center, Single-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multiple-Ascending-Dose Study.Clinical pharmacology in drug development · 2020Trial
- Application of Virtual Twin PBPK Models in Individuals with Obesity via CYP3A4 Phenotyping Using Endogenous Biomarker Data.Clinical pharmacology and therapeutics · 2026Article
- Endogenous biomarkers for assessing CYP3A4 and CYP2D6 activity: A critical review.Drug metabolism and disposition: the biological fate of chemicals · 2026Review
- Article
- Drug-Drug Interaction Risk Assessment Strategies for Biologics in Inflammatory Bowel Disease: A Literature-Based Evidence Mini-Review.Clinical and translational science · 2026Review
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- Interindividual variability in CYP3A-mediated venetoclax metabolism in vitro and in vivo in patients with chronic lymphocytic leukemia.Clinical and translational science · 2024Article
- Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework.Pharmaceutics · 2024Article
- Enzalutamide: Understanding and Managing Drug Interactions to Improve Patient Safety and Drug Efficacy.Drug safety · 2024Review
- Evaluation of the usefulness of plasma 4β-hydroxycholesterol concentration normalized by 4α-hydroxycholesterol for accurate CYP3A phenotyping.Clinical and translational science · 2024Article
- Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Investigation of doxorubicin combined with ciprofloxacin-induced cardiotoxicity: from molecular mechanism to fundamental heart function.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Clinical Evaluation Based on a New Approach to Improve the Accuracy of 4β-Hydroxycholesterol Measurement as a Biomarker of CYP3A4 Activity.Molecules (Basel, Switzerland) · 2023Article
- Formation of CYP3A-specific metabolites of ibrutinib in vitro is correlated with hepatic CYP3A activity and 4β-hydroxycholesterol/cholesterol ratio.Clinical and translational science · 2023Article
- Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio.International journal of molecular sciences · 2022Article
- 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
- Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development.Acta pharmaceutica Sinica. B · 2022Review
- Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThis study aimed to assess changes in the plasma concentrationss of 4β-hydroxycholesterol (4βHC) against intravenous (i.v.) and oral midazolam (MDZ) pharmacokinetics (PK) after administration of a potent CYP3A inhibitor [ketoconazole (KETO)] and inducer [rifampicin (RIF)].
methodsThirty-two healthy subjects (HS) were allocated into three groups of 12 each in KETO and RIF and 10 in a placebo group (PLB). All HS were randomized to receive oral and i.v. MDZ on day 1 or 2 and on day 15 or 16 after receiving RIF (600 mg once daily), KETO (400 mg once daily) or PLB for 2 weeks. Subjects were followed until day 30. The effect of treatments on 4βHC was assessed by analyzing % change from baseline using a linear spline mixed effects model.
resultsCompared with PLB, KETO decreased 4βHC mean values up to 13% (P = 0.003) and RIF increased 4βHC mean values up to 220% (P < 0.001). Within 14 days of stopping KETO and RIF, 4βHC had either returned to baseline (KETO) or was still returning to baseline (RIF). Compared with baseline, mean oral MDZ AUC increased by 11-fold (90% CI ranging from 9-fold to 13-fold increase) and decreased by 92% (90% CI ranging from 90% to 95% decrease) after KETO and RIF, respectively. Similar trends were observed for 6β-hydroxycortisol : cortisol (6βHCL : CL) urinary ratios.
conclusionsChanges in plasma 4βHC can be utilized as a surrogate for MDZ PK after multiple doses of potent CYP3A inducers. There is a more limited dynamic range for 4βHC for assessment of potential CYP3A inhibitors. 4βHC is a valuable tool for the assessment of potential CYP3A inducers in early drug development.
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