PK/PD modellingvancomycinMw\Pharmtherapeutic drug monitoring

For a long time, the Mw\Pharm software suite (MEDI\WARE, Prague, Czech Republic/ Groningen, Netherlands) has been used for PK/PD modeling in therapeutic drug monitoring (TDM). The aim of this study was to find the best model in the newer Windows Mw\Pharm++ 1.3.5.558 version (WIN). 25 patients were repeatedly examined for vancomycin (mean age 63±14 years, body weight 88±21kg, median dose 1g/12 h). Trough concentrations predicted a-posteriori by WIN models “vancomycin_adult_k_C2“, “#vancomycin_adult_C2“, “vancomycin_adult_C2“ were compared with the measured value and “vancomycin adult“ DOS 3.30 model (DOS). Statistics: Percentage prediction error (%PE) calculated as (predicted–measured)/measured values, or WIN-DOS/DOS - data presented as mean±SD, RMSE, Blandt-Altman plot - data presented as bias±SD (95% limits of agreement), Pearson's coefficient of rank correlation (R), Student's t-test. Statistical analysis was performed using GraphPad Prism version 5.00 for Windows. Results : The mean %PE in vancomycin predicted values varied from -4.5%±33.6 to -8.2%±39.3. The %PE between WIN and DOS models varied from -0.2%±24.5% to 4.4±21.4%. Model “vancomycin_adult_C2“ was closest both to measured vancomycin trough concentration and DOS model: %PE -4.5±33.6% vs +4.2±20.3%, RMSE 33.7 vs 20.6, Blandt-Altman bias +2.19±6.17 (-9.9–14.3) vs -0.29± 3.25 (-6.7–6.1), resp. “#vancomycin_adult_C2“ model produced largest %PE (-8.2%), RMSE (40.0) as well as Blandt-Altman bias +2.82±6.76 (-10.4–16.1). The Pearson's R of predicted and measured vancomycin concentration, and of values predicted by WIN and DOS models, varied from 0.5135 to 0.5854, P<0.0001 and from 0.7869 to 0.8462, P<0.0001, resp. Three Windows vancomycin models and one DOS model in the Mw\Pharm software were compared. The best outcomes, i.e. lowest %PE, RMSE and highest Pearson's R, were reached with “vancomycin_adult_C2“ model.

Abstract Background and Objectives : For a long time, the Mw\Pharm software suite (MEDI\WARE, Prague, Czech Republic/ Groningen, Netherlands) has been used for PK/PD modeling in therapeutic drug monitoring (TDM). The aim of this study was to find the best model in the newer Windows Mw\Pharm++ 1.3.5.558 version (WIN). Methods : 25 patients were repeatedly examined for vancomycin (mean age 63±14 years, body weight 88±21kg, median dose 1g/12 h). Trough concentrations predicted a-posteriori by WIN models “vancomycin_adult_k_C2“, “#vancomycin_adult_C2“, “vancomycin_adult_C2“ were compared with the measured value and “vancomycin adult“ DOS 3.30 model (DOS). Statistics: Percentage prediction error (%PE) calculated as (predicted–measured)/measured values, or WIN-DOS/DOS - data presented as mean±SD, RMSE, Blandt-Altman plot - data presented as bias±SD (95% limits of agreement), Pearson's coefficient of rank correlation (R), Student's t-test. Statistical analysis was performed using GraphPad Prism version 5.00 for Windows. Results : The mean %PE in vancomycin predicted values varied from -4.5%±33.6 to -8.2%±39.3. The %PE between WIN and DOS models varied from -0.2%±24.5% to 4.4±21.4%. Model “vancomycin_adult_C2“ was closest both to measured vancomycin trough concentration and DOS model: %PE -4.5±33.6% vs +4.2±20.3%, RMSE 33.7 vs 20.6, Blandt-Altman bias +2.19±6.17 (-9.9–14.3) vs -0.29± 3.25 (-6.7–6.1), resp. “#vancomycin_adult_C2“ model produced largest %PE (-8.2%), RMSE (40.0) as well as Blandt-Altman bias +2.82±6.76 (-10.4–16.1). The Pearson's R of predicted and measured vancomycin concentration, and of values predicted by WIN and DOS models, varied from 0.5135 to 0.5854, P<0.0001 and from 0.7869 to 0.8462, P<0.0001, resp. Conclusions : Three Windows vancomycin models and one DOS model in the Mw\Pharm software were compared. The best outcomes, i.e. lowest %PE, RMSE and highest Pearson's R, were reached with “vancomycin_adult_C2“ model.