Trial reportClinical pharmacokinetics2024
The OCT2/MATE1 Interaction Between Trifluridine, Metformin and Cimetidine: A Crossover Pharmacokinetic Study.
Trial report in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Metformin in Colorectal Cancer: Epidemiological Evidence, Predictive Biomarkers, and Implications for Prevention and Treatment.International journal of molecular sciences · 2025Review
- Pseudo acute kidney injury in patients receiving CDK4/6 inhibitors.British journal of cancer · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesTrifluridine/tipiracil, registered for the treatment of patients with metastatic gastric and colorectal cancer, is a substrate and inhibitor for the organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion protein 1 (MATE1), which raises the potential for drug-drug interactions with other OCT2/MATE1 modulators. Therefore, we prospectively examined the effect of an OCT2/MATE1 inhibitor (cimetidine) and substrate (metformin) on the pharmacokinetics of trifluridine.
methodsIn this three-phase crossover study, patients with metastatic colorectal or gastric cancer were sequentially treated with trifluridine/tipiracil alone (phase A), trifluridine/tipiracil concomitant with metformin (phase B) and trifluridine/tipiracil concomitant with cimetidine (phase C). The primary endpoint was the relative difference in exposure of trifluridine assessed by the area under the curve from timepoint zero to infinity. A > 30% change in exposure was considered clinically relevant. A p-value of < 0.025 was considered significant because of a Bonferroni correction.
resultsEighteen patients were included in the analysis. Metformin did not significantly alter the exposure to trifluridine (- 12.6%; 97.5% confidence interval - 25.0, 1.8; p = 0.045). Cimetidine did alter the exposure to trifluridine significantly (+ 18.0%; 97.5% confidence interval 4.5, 33.3; p = 0.004), but this increase did not meet our threshold for clinical relevance. Metformin trough concentrations were not influenced by trifluridine/tipiracil.
conclusionsOur result suggests that the OCT2/MATE1 modulators cimetidine and metformin can be co-administered with trifluridine/tipiracil without clinically relevant effects on drug exposure. CLINICAL
trial registrationNL8067 (registered 04-10-2019).
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