ArticleClinical pharmacology and therapeutics2019
Prediction of the Impact of Cytochrome P450 2C9 Genotypes on the Drug-Drug Interaction Potential of Siponimod With Physiologically-Based Pharmacokinetic Modeling: A Comprehensive Approach for Drug Label Recommendations.
Article in Clinical pharmacology and therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Physiologically based pharmacokinetic (PBPK) modelling of tamsulosin related to CYP2D6*10 allele.Archives of pharmacal research · 2021Trial
- Siponimod pharmacokinetics, safety, and tolerability in combination with the potent CYP3A4 inhibitor itraconazole in healthy subjects with different CYP2C9 genotypes.European journal of clinical pharmacology · 2019Trial
- PBPK Modeling and Clinical Data Reveal Reduced Impact of CYP3A4 and CYP2C9 Inhibitors on Elimination of Siponimod.Clinical and translational science · 2026Article
- Efavirenz and CYP2C9 Genetic Polymorphisms Reduce CYP2C9 Activity in Healthy Participants.Clinical and translational science · 2026Article
- Machine learning models for drug-drug interaction prediction from computational discovery to clinical application.NPJ digital medicine · 2026Review
- The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination.Multiple sclerosis and related disorders · 2023Review
- Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective.Pharmaceutical research · 2022Review
- Article
- Pharmacokinetic Characteristics of Siponimod in Healthy Volunteers and Patients With Multiple Sclerosis: Analyses of Published Clinical Trials.Frontiers in pharmacology · 2022Article
- Clinical Evaluation of Siponimod for the Treatment of Secondary Progressive Multiple Sclerosis: Pathophysiology, Efficacy, Safety, Patient Acceptability and Adherence.Patient preference and adherence · 2022Review
- Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis.Journal of personalized medicine · 2021Review
- Reviewing Data Integrated for PBPK Model Development to Predict Metabolic Drug-Drug Interactions: Shifting Perspectives and Emerging Trends.Frontiers in pharmacology · 2021Review
- Siponimod: A Review in Secondary Progressive Multiple Sclerosis.CNS drugs · 2020Review
- Gaining First Insights on Secondary Progressive Multiple Sclerosis Patients Treated With Siponimod in Clinical Routine: Protocol of the Noninterventional Study AMASIA.JMIR research protocols · 2020Article
- Identification and ranking of important bio-elements in drug-drug interaction by Market Basket Analysis.BioImpacts : BI · 2020Article
- Siponimod: First Global Approval.Drugs · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We predicted the drug-drug interaction (DDI) potential of siponimod in presence of cytochrome P450 (CYP)2C9/CYP3A4 inhibitors/inducers in subjects with different CYP2C9 genotypes by physiologically-based pharmacokinetic (PK) modeling. The model was established using in vitro and clinical PK data and verified by adequately predicting siponimod PK when coadministered with rifampin. With strong and moderate CYP3A4 inhibitors, an increased DDI risk for siponimod was predicted for CYP2C9*3/*3 genotype vs. other genotypes area under the curve ratio (AUCR): 3.03-4.20 vs. ≤ 1.49 for strong; 2.42 vs. 1.14-1.30 for moderate. AUCRs increased with moderate (2.13-2.49) and weak (1.12-1.42) CYP3A4/CYP2C9 inhibitors to the same extent for all genotypes. With strong CYP3A4/moderate CYP2C9 inducers and moderate CYP3A4 inducers, predicted AUCRs were 0.21-0.32 and 0.35-0.71, respectively. This complementary analysis to the clinical PK-DDI studies confirmed the relevant influence of CYP2C9 polymorphism on the DDI behavior of siponimod and represented the basis for the DDI labeling recommendations.
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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.