Trial reportEuropean journal of clinical pharmacology2014
Comparison of two endogenous biomarkers of CYP3A4 activity in a drug-drug interaction study between midostaurin and rifampicin.
Trial report in European 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 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- Safety, tolerability, and pharmacokinetics of a single ascending subcutaneous dose of GSK3772847 in healthy participants.Pharmacology research & perspectives · 2023Trial
- GLPG1205, a GPR84 Modulator: Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Subjects.Clinical pharmacology in drug development · 2021Trial
- Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients.British journal of pharmacology · 2021Trial
- Endogenous biomarkers for assessing CYP3A4 and CYP2D6 activity: A critical review.Drug metabolism and disposition: the biological fate of chemicals · 2026Review
- Application of Virtual Twin PBPK Models in Individuals with Obesity via CYP3A4 Phenotyping Using Endogenous Biomarker Data.Clinical pharmacology and therapeutics · 2026Article
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- Dynamic phenotype monitoring to prevent genotype-phenotype discrepancies in pharmacogenetic-guided drug therapy.Frontiers in pharmacology · 2026Review
- Precision medication based on the evaluation of drug metabolizing enzyme and transporter functions.Precision clinical medicine · 2025Review
- The effect of carbamazepine, a strong CYP3A inducer, on the pharmacokinetics of zongertinib in healthy male volunteers.Pharmacotherapy · 2025Article
- Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework.Pharmaceutics · 2024Article
- 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
- The Effect of Modafinil on the Safety and Pharmacokinetics of Lorlatinib: A Phase I Study in Healthy Participants.Clinical pharmacokinetics · 2021Article
- The Protein Kinase Inhibitor Midostaurin Improves Functional Neurological Recovery and Attenuates Inflammatory Changes Following Traumatic Cervical Spinal Cord Injury.Biomolecules · 2021Article
- Evaluation of 1β-Hydroxylation of Deoxycholic Acid as a Non-Invasive Urinary Biomarker of CYP3A Activity in the Assessment of Inhibition-Based Drug-Drug Interaction in Healthy Volunteers.Journal of personalized medicine · 2021Article
- Population Pharmacokinetic Analysis of Quizartinib in Healthy Volunteers and Patients With Relapsed/Refractory Acute Myeloid Leukemia.Journal of clinical pharmacology · 2020Article
- Development and validation of a method for the simultaneous quantification of endogenous steroids metabolized by CYP3A.Translational and clinical pharmacology · 2020Article
- Drug-metabolizing enzymes CYP3A as a link between tacrolimus and vitamin D in renal transplant recipients: is it relevant in clinical practice?Pediatric nephrology (Berlin, Germany) · 2019Review
- Effect of Grapefruit Juice Intake on Serum Level of the Endogenous CYP3A4 Metabolite 4β-Hydroxycholesterol-an Interaction Study in Healthy Volunteers.The AAPS journal · 2019Article
- Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment.Clinical pharmacology : advances and applications · 2019Article
- The effect of itraconazole and rifampicin on the pharmacokinetics of osimertinib.British journal of clinical pharmacology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMidostaurin, a multitargeted tyrosine kinase inhibitor, is primarily metabolized by CYP3A4. This midostaurin drug-drug interaction study assessed the dynamic response and clinical usefulness of urinary 6β-hydroxycortisol to cortisol ratio (6βCR) and plasma 4β-hydroxycholesterol (4βHC) for monitoring CYP3A4 activity in the presence or absence of rifampicin, a strong CYP3A4 inducer.
methodsForty healthy adults were randomized into groups for either placebo or treatment with rifampicin 600 mg QD for 14 days. All participants received midostaurin 50 mg on day 9. Midostaurin plasma pharmacokinetic parameters were assessed. Urinary 6βCR and plasma 4βHC levels were measured on days 1, 9, 11, and 15.
resultsBoth markers remained stable over time in the control group and increased significantly in the rifampicin group. In the rifampicin group, the median increases (vs day 1) on days 9, 11, and 15 were 4.1-, 5.2-, and 4.7-fold, respectively, for 6βCR and 3.4-, 4.1-, and 4.7-fold, respectively, for 4βHC. Inter- and intrasubject variabilities in the control group were 45.6 % and 30.5 %, respectively, for 6βCR, and 33.8 % and 7.5 %, respectively, for 4βHC. Baseline midostaurin area under the concentration-time curve (AUC) correlated with 4βHC levels (ρ = -0.72; P = .003), but not with 6βCR (ρ = 0.0925; P = .6981).
conclusionsBoth 6βCR and 4βHC levels showed a good dynamic response range upon strong CYP3A4 induction with rifampicin. Because of lower inter- and intrasubject variability, 4βHC appeared more reliable and better predictive of CYP3A4 activity compared with 6βCR. The data from our study further support the clinical utility of these biomarkers.
Indexed as
Identifiers
What OpenQuestion holds
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.