Trial reportClinical pharmacokinetics2019
Effect of Fluconazole Coadministration and CYP2C9 Genetic Polymorphism on Siponimod Pharmacokinetics in Healthy Subjects.
Trial report in Clinical pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06639282 (SIPO1-AD), which is not on this map. Cited by 14 papers.
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.
SIPO1-AD: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients With Mild Alzheimer's Disease
Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- 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
- Drug Transporters and Metabolizing Enzymes in Antimicrobial Drug Pharmacokinetics: Mechanisms, Drug-Drug Interactions, and Clinical Implications.Biomolecules · 2025Review
- Doses Evaluated in Clinical Pharmacology Studies Investigating the Effect of Intrinsic and Extrinsic Factors on PK and Safety: Case Examples from Approved Drug Development Programs.The AAPS journal · 2024Review
- Recombinant Technologies Facilitate Drug Metabolism, Pharmacokinetics, and General Biomedical Research.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination.Multiple sclerosis and related disorders · 2023Review
- 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
- 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
- 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.Clinical pharmacology and therapeutics · 2019Article
- Design and Synthesis of Novel 1,3-Thiazole and 2-Hydrazinyl-1,3-Thiazole Derivatives as Anti-Molecules (Basel, Switzerland) · 2019Article
- Siponimod: First Global Approval.Drugs · 2019Article
- Siponimod pharmacokinetics, safety, and tolerability in combination with rifampin, a CYP2C9/3A4 inducer, in healthy subjects.European 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
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe aim of this study was to assess the pharmacokinetics (PK) and safety/tolerability of siponimod in healthy subjects when coadministered with (1) the moderate cytochrome P450 (CYP) 2C9 and CYP3A inhibitor fluconazole (Study A), and (2) with three different CYP2C9 genotype variants (Study B).
methodsStudy A was an open-label, single-dose study comprising periods 1 (14 days; day 1: siponimod 4 mg) and 2 (20 days; day 1: fluconazole 200 mg twice daily; days 2-19: fluconazole 200 mg once daily; day 3: siponimod 4 mg) in healthy subjects (n = 14) with the wild-type CYP2C9 genotype (CYP2C9*1/*1). Study B was a multicentre, open-label study comprising parts 1 (day 1: siponimod 0.25 mg once daily in the CYP2C9*1/*1, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes) and 2 (days 1-2: 0.25 mg once daily; day 3: 0.5 mg once daily in the CYP2C9*2/*3 and CYP2C9*3/*3 genotypes only) in healthy subjects with polymorphic variants of CYP2C9 (n = 24). Pharmacokinetic parameters were calculated using noncompartmental methods.
resultsIn Study A, coadministration with fluconazole produced an approximately twofold increase in mean area under the curve (AUC) versus siponimod alone (from 1110 to 2160 h*ng/mL), and an increase in maximum plasma concentration (C
conclusionsChanges in siponimod PK, when coadministered with fluconazole at steady-state and in subjects with different CYP2C9 genotypes, indicate that the reduced CYP2C9 enzymatic activity does not affect the absorption phase of siponimod but prolongs the elimination phase. These results confirm the relevance of CYP2C9 activity on siponimod metabolism in humans.
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