www.klinickafarmakologie.cz / Klin Farmakol Farm 2022;36(3):85-92 / KLINICKÁ FARMAKOLOGIE A FARMACIE 87 ORIGINÁLNÍ PRÁCE COMPARISON OF MW\PHARM 3.30 (DOS) AND MW\PHARM ++ (WINDOWS) VERSIONS OF PHARMACOKINETIC SOFTWARE FOR PK/PD MODELLING OF VANCOMYCIN IN CONTINUOUS ADMINISTRATION The formula is based on the assumptions that CL is related to the CLcr and CLm is linearly related to BSA. CLcr is calculated by Jelliffe II equation (9). BSA is calculated according to Du Bois and Du Bois (10). The “#vancomycin_adult_k_C2” model (WIN1) uses renal (kelr) and metabolic (kelm) elimination rate constants instead of fr or Clm, respectively. The parameters were converted by Formula 2 and Formula 3, respectively, fr = kelr * V1 * LBMc * 1000 * 1.73 (2) 60 BSA C1m = kelm * V1 * LBMc * 1.85 (3) BSA V1 represents the volume of distribution and LBMc is lean body mass corrected for fat distribution calculated according to Chennavasin (11). The population-based parameters of all the models are given in Table 2. The Marquardt algorithm was used for extrapolation. Examples for graphical output of DOS1 andWIN3 models are shown in Add Fig. 1 and Add Fig. 2, respectively. Model evaluation Concentrations predicted by the “vancomycin (cont.inf.) %ahz” (DOS1) and “vancomycin adult” (DOS2) DOS models and by the “#vancomycin_adult_k_C2” (WIN1), “#vancomycin_adult_C2” (WIN2), “vancomycin_adult_C2” (WIN3), and “vancomycin_C1” (WIN4) Windows models were compared with the measured concentration and the concentration predicted by the DOS1 model. All models were two-compartmental, with the exception of WIN4 which is one-compartmental. Predictions by all models were evaluated retrospectively. Percentage prediction error (%PE), RMSE, and Bland-Altman plot were used for prediction precision evaluation. %PE was calculated as the difference between the predicted and the measured value (Formula 4), or as the difference between models (Formula 5). RMSE was calculated according to Formula 6. %PE = predicted –measured (4) measured %PE = predicted (WIN) – predicted (D0S1) (5) predicted (D0S1) RMSE = 1 × Σ(%PE)2 (6) N All values are presented as mean ± standard deviation (SD). Due to normal distribution of values, statistical analysis was performed by using paired Student’s t-test. The Prism 5.0 software by GraphPad Software was used for statistical analysis (Pearson’s R, Student’s t-test, Bland-Altman plot). Results Best model selection Vancomycin concentrations predicted by all models are shown in Fig. 1. Mean concentrations predicted by the models were significantly lower than the measured concentrations (Table 3). Mean values of %PE varied from −3.2 in DOS2 to −20.8% in WIN4. Add Fig. 1. Graphical output of DOS1 model Add Fig. 2. Graphical output of WIN3 model
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