Dabigatran etexilate is a direct oral anticoagulant (thrombin inhibitor) used for the prevention of stroke and systemic thromboembolic events in patients with permanent atrial fibrillation; prevention of venous thromboembolic events and deep veins thrombosis; treatment and prevention of pulmonary embolism. Dabigatran is a relatively new drug, and as a result, its interactions with other medications and their significance are not fully known. A 72 years old male, having a medical history of heart and renal failure, was hospitalized for pneumonia treatment. The patient was taking several drugs, including dabigatran 150 mg twice daily and ranolazine 750 mg twice daily. His creatinine clearance was 45.22 mL/min, International Normalized Ratio (INR)-7.03. Dabigatran was discontinued. After 9 days, INR decreased to 1.33, and after 6 days, creatinine clearance increased to 64.39 mL/min. The patient was taking an adequate dosage of dabigatran, thus dabigatran was thought to be overdosed due to its interaction with ranolazine because dabigatran is a p-glycoprotein substrate, whereas ranolazine is the inhibitor of this transporter. Dabigatran and ranolazine should be used with caution in patients with renal failure. It is recommended to use smaller doses of both medications and observe coagulation parameters if needed.

The glomerular filtration rate (GFR), according to which the drug dose for patients with chronic kidney disease (CKD) is adjusted, is computed with estimators (eGFR) that are developed specifically for CKD. These particular types of estimators are also used in population pharmacokinetic (pop PK) modelling in drug development. Similar approaches without scientific validation have been proposed for patients with acute kidney injury (AKI), yet it is uncertain which specific eGFR should be used for drug dosing or in pop PK models in patients with AKI. In our study, we included 34 patients with AKI and vancomycin (VCM) treatment, and we built both individual PK and pop PK (non-linear mixed-effects, one-compartment) models to see which eGFR estimator is the best covariate. In these models different eGFRs (Cockcroft-Gault, MDRD, CKD-EPI 2009, Jelliffe and Jelliffe, Chen et al., and Yashiro et al. 2013) were used. We included six additional patients to validate the final pop PK model. All eGFRs underrate the true renal clearance in the AKI, so we created pop PK models for VCM dosing in AKI with all eGFRs, to discover that the most accurate model was the one with the Cockcroft-Gault estimator. Since the eGFRs underestimate the true renal clearance in AKI, they are inaccurate for clinical drug dosing decisions, with the exception of the Cockcroft-Gault one, which is appropriate for the pop PK models intended for drug development purposes in AKI.