Trial reportEuropean journal of drug metabolism and pharmacokinetics2018
Effects of Metformin and Furosemide on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Implications for Their Use as Probe Drugs in a Transporter Cocktail.
Trial report in European journal of drug metabolism and pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02574845 (The Effect of Different Doses of Metformin or Furosemide on Rosuvastatin Pharmacokinetics Following Oral Administration in Healthy Male Subjects), which is not on this map. Cited by 15 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.
The Effect of Different Doses of Metformin or Furosemide on Rosuvastatin Pharmacokinetics Following Oral Administration in Healthy Male Subjects (an Open-label, Randomised, Single-dose, Six-way Crossover Study)
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Pharmacokinetics of Rosuvastatin: A Systematic Review of Randomised Controlled Trials in Healthy Adults.Clinical pharmacokinetics · 2021Pooled it
- Validation of a Drug Transporter Probe Cocktail Using the Prototypical Inhibitors Rifampin, Probenecid, Verapamil, and Cimetidine.Clinical pharmacokinetics · 2020Trial
- Optimization of a drug transporter probe cocktail: potential screening tool for transporter-mediated drug-drug interactions.British journal of clinical pharmacology · 2018Trial
- Biomarker-Based Prediction of OATP1B1 Activity in Clinical Routine-Investigating Coproporphyrins as Markers for Drug-Drug-Gene Interactions.Clinical pharmacology and therapeutics · 2026Article
- Prevalence of substances with OATP1B1 inhibitory properties in individual case safety reports of suspected statin-associated myopathy - an analysis of Swiss pharmacovigilance data.European journal of clinical pharmacology · 2026Article
- Lack of Modulation of In Vivo Activity of Organic Anion Transporters 1 and 3 in Pregnancy Using Furosemide as a Probe.Journal of clinical pharmacology · 2026Article
- Effect of vepdegestrant, a PROTAC oestrogen receptor degrader, on dabigatran and rosuvastatin pharmacokinetics in healthy participants.British journal of clinical pharmacology · 2025Article
- Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach.Cancer chemotherapy and pharmacology · 2021Article
- Physiologically Based Pharmacokinetic Modeling of Rosuvastatin to Predict Transporter-Mediated Drug-Drug Interactions.Pharmaceutical research · 2021Article
- Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous.Scientific reports · 2021Article
- Metformin and statin use associate with plasma proteinBMJ open diabetes research & care · 2020Article
- Physiologically-Based Pharmacokinetic Models for Evaluating Membrane Transporter Mediated Drug-Drug Interactions: Current Capabilities, Case Studies, Future Opportunities, and Recommendations.Clinical pharmacology and therapeutics · 2020Review
- Clinical Studies on Drug-Drug Interactions Involving Metabolism and Transport: Methodology, Pitfalls, and Interpretation.Clinical pharmacology and therapeutics · 2019Review
- Probe Cocktail to Assess Transporter Function in Sandwich-Cultured Human Hepatocytes.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2019Article
- Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Mass Spectrometry for Therapeutic Drug Monitoring of Metformin and Rosuvastatin in Human Plasma.Molecules (Basel, Switzerland) · 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
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn a recently described probe drug cocktail for clinically relevant drug transporters containing digoxin, furosemide, metformin and rosuvastatin, mutual interactions were essentially absent except for increases in the systemic exposure of rosuvastatin. To optimize the cocktail, we further examined the dose dependence of the effects of metformin and furosemide on rosuvastatin pharmacokinetics.
methodsThis was a randomized, open label, single center, six-treatment, six-period, six-sequence crossover trial. Eighteen healthy male subjects received 10 mg rosuvastatin as reference treatment and, as test treatments, 10 mg rosuvastatin combined with 10, 50 or 500 mg metformin (T1, T2 and T3) or with 1 or 5 mg furosemide (T4 and T5). Primary pharmacokinetic endpoints were rosuvastatin C
resultsThe relative bioavailability of rosuvastatin was essentially unchanged when administered with metformin in T1 and T2, but in T3 it increased to 152% for AUC
conclusionThe increased systemic exposure of rosuvastatin when administered as part of the proposed transporter cocktail is most likely attributable to metformin and only to a minor degree to furosemide. Reduction of the doses of metformin and furosemide is expected to eliminate the previously described interaction. EudraCT no. 2015-003052-46, ClinicalTrials.gov identifier NCT02574845.
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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.