Trial reportClinical pharmacokinetics2016
Effects of Cytochrome P450 3A4 Inhibitors-Ketoconazole and Erythromycin-on Bitopertin Pharmacokinetics and Comparison with Physiologically Based Modelling Predictions.
Trial report in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Advancements in Virtual Bioequivalence: A Systematic Review of Computational Methods and Regulatory Perspectives in the Pharmaceutical Industry.Pharmaceutics · 2024Review
- Pharmacokinetic profile of bitopertin, a selective GlyTNaunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Computational Approaches in Preclinical Studies on Drug Discovery and Development.Frontiers in chemistry · 2020Review
- Genetic analysis of drug metabolizing phase-I enzymes CYP3A4 in Tibetan populations.Journal of genetics · 2017Article
- Progress in Prediction and Interpretation of Clinically Relevant Metabolic Drug-Drug Interactions: a Minireview Illustrating Recent Developments and Current Opportunities.Current pharmacology reports · 2017Review
- A Cytochrome P450 3A4 Biosensor Based on Generation 4.0 PAMAM Dendrimers for the Detection of Caffeine.Biosensors · 2016Article
- Management of hair loss associated with endocrine therapy in patients with breast cancer: an overview.SpringerPlus · 2016Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo assess the effect of strong and moderate cytochrome P450 (CYP) 3A4 inhibition on exposure of bitopertin, a glycine reuptake inhibitor primarily metabolized by CYP3A4, and to compare the results with predictions based on physiologically based pharmacokinetic (PBPK) modelling.
methodsThe effects of ketoconazole and erythromycin were assessed in two male volunteer studies with open-label, two-period, fixed-sequence designs. Twelve subjects were enrolled in each of the studies. In period 1, a single dose of bitopertin was administered; in period 2, 400 mg ketoconazole was administered once daily for 17 days or 500 mg erythromycin was administered twice daily for 21 days. A single dose of bitopertin was coadministered on day 5. Pharmacokinetic parameters were derived by non-compartmental methods. Simulated bitopertin profiles using dynamic PBPK modelling for a typical healthy volunteer in GastroPlus(®) were used to predict changes in pharmacokinetic parameters.
resultsIn healthy volunteers, coadministration of ketoconazole increased the bitopertin area under the plasma concentration-time curve (AUC) from 0 to 312 h (AUC0-312h) 4.2-fold (90 % confidence interval [CI] 3.5-5.0) and erythromycin increased the AUC from time zero to infinity (AUC0-inf) 2.1-fold (90 % CI 1.9-2.3). The peak concentration (C max) increased by <25 % in both studies. Simulated bitopertin profiles using PBPK modelling showed good agreement with the observed AUC ratios in both studies. The predicted AUC0-inf ratios for the interaction with ketoconazole and erythromycin were 7.7 and 1.9, respectively.
conclusionStrong CYP3A4 inhibitors increase AUC0-inf of bitopertin 7- to 8-fold and hence should not be administered concomitantly with bitopertin. Moderate CYP3A4 inhibitors double AUC0-inf.
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