Background and Importance Digoxin is a drug with a narrow therapeutic index (0.8-1.2 ng/mL). Therapeutic drug monitoring is an important tool to improve therapeutic safety and efficacy, especially in elderly patients.

Aim and Objectives To estimate the accuracy and precision of three pharmacokinetic software to analyse serum digoxin concentrations (SDC).

Material and Methods Retrospective observational study in elderly patients admitted to a tertiary hospital and treated with digoxin in 2020. We excluded patients over 80 years-old. Variables recorded: sex, age, body mass index (BMI), SDC, creatinine clearance evaluated by the Cockcroft-Gault equation (CrCl), and concomitant treatment: proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs).

SDC were estimated with three pharmacokinetic software: Mediware, PKS and NONMEM.

Accuracy and precision were assessed using Sheiner and Beal's prediction error theory. Accuracy with the mean prediction error (MPE) and precision with the mean absolute prediction error (MPAE) and the square root of the root mean square prediction error (RMSE).

Two subgroups were analysed: renal impairment patients (CrCl<60mL/min) and patients with two or more SDC.

Results 53 patients with 130 SDC, 31 women (58.5%), median age 75.5 years-old (66.5-80.7). 64% on concomitant treatment with PPIs and 41.5% with NSAIDs.

Accuracy: MPE 0.002, -0.011, -0.081, for Mediware, PKS and NONMEM respectively.

Precision: MPAE 0.193, 0.201, 0.243; RMSE 0.331, 0.345, 0.328 for Mediware, PKS and NONMEM.

Renal impairment: 32 patients with 64 levels.

Accuracy: MPE -0.052, -0.028, -0.106 for Mediware, PKS and NONMEM.

Precision: MPAE 0.192, 0.246, 0.275; RMSE 0.330, 0.416, 0.363 for Mediware, PKS and NONMEM.

≥2 levels: 36 patients

Accuracy: MPE 0.003, -0.010, -0.080 for Mediware, PKS and NONMEM.

Precision: MPAE 0.205, 0.211, 0.235; RMSE 0.347, 0.360, 0.312 for Mediware, PKS and NONMEM.

Conclusion and Relevance The three software showed similar accuracy and precision for analysing SDC.

Mediware is the best tool for daily clinical practice in terms of ease of use.

Conflict of Interest No conflict of interest