Trial reportEuropean journal of clinical pharmacology2014
Investigation of combined CYP3A4 inductive/inhibitory properties by studying statin interactions: a model study with the renin inhibitor ACT-178882.
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 3 papers, 1 of them a synthesis that pooled it.
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
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Intrinsic Factors Influencing Simvastatin and Simvastatin Acid Pharmacokinetics: Age-Related Studies in Thai Adults and Cross-Population Comparisons.Clinical and translational science · 2026Pooled it
- Verification of a Physiologically-based Pharmacokinetic Model for Predicting CYP3A4-mediated Simvastatin and Simvastatin Acid Drug-drug Interactions.The AAPS journal · 2026Article
- Current Evidence, Challenges, and Opportunities of Physiologically Based Pharmacokinetic Models of Atorvastatin for Decision Making.Pharmaceutics · 2021Review
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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeACT-178882, a direct renin inhibitor, was used as a model compound in an elaborate drug-drug interaction study with atorvastatin and simvastatin to explore complex CYP3A4 inductive and inhibitory properties.
methodsThirty-two healthy male subjects received single doses of 20 mg atorvastatin and 20 mg simvastatin on days 1, 9, 31, and 41. On days 6 to 33, 500 mg ACT-178882 was administered once daily. Plasma concentrations of ACT-178882, simvastatin, and atorvastatin were measured by LC-MS/MS. Routine safety assessments were performed throughout the study.
resultsExposure (as based on area under the curve) to simvastatin and 6β-hydroxyacid simvastatin increased (90 % confidence interval) 4.63-fold (3.90, 5.50) and 3.71-fold (3.19, 4.32), respectively, when comparing day 9 and day 1. On day 9, exposure to atorvastatin was similar but Cmax decreased, while both variables decreased for ortho-hydroxy atorvastatin when compared to day 1. On day 31, after prolonged administration of ACT-178882, exposure to atorvastatin, ortho-hydroxy atorvastatin, simvastatin, and 6β-hydroxyacid simvastatin decreased by 14, 19, 21, and 27 %, respectively, when compared to day 9. However, on this day, exposure to simvastatin and its metabolite was still markedly higher when compared to day 1. Effects of ACT-178882 had largely dissipated on day 41.
conclusionsThis design enabled the study of complex time-dependent effects on CYP3A4 activity with clinically relevant substrates.
Indexed as
Identifiers
24728182What 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.