ArticleEuropean journal of drug metabolism and pharmacokinetics2026
Model-Based Evaluation of the Warfarin-Sulfamethoxazole Drug-Drug Interaction.
Article in European journal of drug metabolism and pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
BACKGROUND AND
objectiveWarfarin exhibits complex drug-drug interactions (DDIs), particularly with sulfamethoxazole, which competitively inhibits cytochrome P450 2C-mediated metabolism of S-warfarin. This study developed a population pharmacokinetic-pharmacodynamic (PK-PD) model to evaluate the DDI of warfarin with different doses of sulfamethoxazole/trimethoprim using a model-based approach.
methodsMale Wistar rats (n = 4 per group) received intravenous warfarin (400 μg/kg) with or without therapeutic or standard prophylactic doses of sulfamethoxazole/trimethoprim (200/40 mg/kg and 100/20 mg/kg, respectively). Plasma concentrations of S-warfarin and sulfamethoxazole and the prothrombin time international normalized ratio (PT-INR) were recorded. After developing a population PK-PD model of the interaction between S-warfarin and sulfamethoxazole, simulations were conducted with a target trough PT-INR of 2.0 at steady state. The required warfarin dose was compared between the WF alone, WF+TD-ST (ST 200/40 mg/kg), WF+SPD-ST (ST 100/20 mg/kg), and WF+LPD-ST (ST 20/4 mg/kg) groups.
resultsAmong the groups, the WF+TD-ST group exhibited the highest S-warfarin AUC
conclusionThe proposed model supports model-based warfarin dosing during co-administration with different doses of sulfamethoxazole/trimethoprim.
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Registered trials
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