Trial reportEuropean journal of clinical pharmacology2013
Almorexant effects on CYP3A4 activity studied by its simultaneous and time-separated administration with simvastatin and atorvastatin.
Trial report in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Intrinsic Factors Influencing Simvastatin and Simvastatin Acid Pharmacokinetics: Age-Related Studies in Thai Adults and Cross-Population Comparisons.Clinical and translational science · 2026Pooled it
- Absence of pharmacokinetic and pharmacodynamic interactions between almorexant and warfarin in healthy subjects.Drugs in R&D · 2013Trial
- Utilizing Physiologically Based Pharmacokinetic Modeling and Virtual Simulation for Simvastatin Tablets to Evaluate the Sensitivity of Using Parent vs Metabolite as Analyte on Bioequivalence Assessment.The AAPS journal · 2025Article
- Current and novel dual orexin receptor antagonists for the treatment of insomnia: the emergence of vornorexant.The international journal of neuropsychopharmacology · 2025Review
- Current Evidence, Challenges, and Opportunities of Physiologically Based Pharmacokinetic Models of Atorvastatin for Decision Making.Pharmaceutics · 2021Review
- Prediction of Cyclosporin-Mediated Drug Interaction Using Physiologically Based Pharmacokinetic Model Characterizing Interplay of Drug Transporters and Enzymes.International journal of molecular sciences · 2020Article
- Pharmacokinetic interactions between simvastatin and setipiprant, a CRTH2 antagonist.European journal of clinical pharmacology · 2015Article
- Pharmacokinetic drug-drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management.Therapeutics and clinical risk management · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo characterise further the previously observed cytochrome P450 3A4 (CYP3A4) interaction of the dual orexin receptor antagonist almorexant.
methodsPharmacokinetic interactions were investigated (n = 14 healthy male subjects in two treatment groups) between almorexant at steady-state when administered either concomitantly or 2 h after administration of single doses of simvastatin (40 mg) or atorvastatin (40 mg).
resultsAlmorexant dose-dependently increased simvastatin exposure (AUC0-∞) when administered concomitantly [geometric mean ratios (90 % CI): 2.5 (2.1, 2.9) (100 mg), 3.9 (3.3, 4.6) (200 mg)], but not Cmax [3.7 (3.0, 4.5) for both doses]. Time-separated administration resulted in relevant reductions of the interaction [AUC0-∞: 1.4 (1.2, 1.7) (100 mg), 1.7 (1.5, 2.0) (200 mg); Cmax: 1.5 (1.3, 1.9) (100 mg), 1.9 (1.6, 2.4) (200 mg)]. Similar results were obtained for hydroxyacid simvastatin. Independent of almorexant dose and relative time of administration, AUC0-∞ and Cmax of atorvastatin increased (ratios ranged from 1.1 to 1.5). AUC0-∞ and Cmax of o-hydroxy atorvastatin decreased dose-independently [AUC0-∞: 0.8 (0.8, 0.9) (100 mg), 0.6 (0.5, 0.6) (200 mg); Cmax: 0.3 (0.3, 0.4) (100 mg), 0.2 (0.2, 0.3) (200 mg)] when atorvastatin was concomitantly administered. Cmax of o-hydroxy atorvastatin slightly decreased (0.8 for both doses) following time-separated administration; AUC0-∞ was unchanged.
conclusionsWhereas almorexant increased simvastatin exposure dose- and relative time of administration-dependently, atorvastatin exposure increased to a smaller extent and irrespective of dose and time. This suggests that the observed interaction of almorexant with simvastatin is mainly caused by intestinal CYP3A4 inhibition, whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition.
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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.