Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy · 2025
Development and external validation of a population pharmacokinetic model and optimal Vancomycin dosing regimen for overweight and obese patients.
СтатьяВалидационное исследованиеНазвание и аннотация: Перевод в очереди
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Komatsu Toshiaki, Tomizawa Atsushi, Samura Masaru, Suzuki Ayako, Ishigo Tomoyuki, Fujii Satoshi, Ibe Yuta, Yoshida Hiroaki, Tanaka Hiroaki, Fujihara Hisato, Yamaguchi Fumihiro, Ebihara Fumiya, Maruyama Takumi, Yagi Yusuke, Hamada Yukihiro, Nagumo Fumio, Takuma Akitoshi, Chiba Hiroaki, Nishi Yoshifumi, Igarashi Yuki, Enoki Yuki, Otori Katsuya, Matsumoto Kazuaki
Аннотация
INTRODUCTION: This study aimed to develop and evaluate a population pharmacokinetic model and optimal dosing regimen for vancomycin in overweight and obese adults.
METHODS: A population pharmacokinetic model using a two-compartment system was constructed using a nonlinear mixed-effects approach, incorporating 527 data points from 184 participants. External validation of the model was carried out using an additional 55 data points from 21 participants; these were not used in the construction of the model. Monte Carlo simulations were used to determine the dosage that achieved the steady state area under the curve value falling between 400 μg h/mL and 600 μg h/mL.
RESULTS: In the final model, vancomycin clearance was found to be a significant predictor of blood vancomycin levels, alongside creatinine clearance (CCr), blood urea nitrogen levels, and incidence of heart failure. CCr was calculated with adjusted body weight (AdjBW). AdjBW was selected as a predictor of the volume of distribution in the central and peripheral compartments. External validation showed that the highest proportion of cases had deviations of less than 15 % between measured and predicted values in the final model developed in this study. This indicates that our model outperforms previously developed models (five for obese patients and four for non-obese patients).
CONCLUSIONS: Our model shows that determining effective vancomycin doses for overweight and obese patients depend on estimated CCr rates, AdjBW, BUN levels, and incidence of heart failure.
METHODS: A population pharmacokinetic model using a two-compartment system was constructed using a nonlinear mixed-effects approach, incorporating 527 data points from 184 participants. External validation of the model was carried out using an additional 55 data points from 21 participants; these were not used in the construction of the model. Monte Carlo simulations were used to determine the dosage that achieved the steady state area under the curve value falling between 400 μg h/mL and 600 μg h/mL.
RESULTS: In the final model, vancomycin clearance was found to be a significant predictor of blood vancomycin levels, alongside creatinine clearance (CCr), blood urea nitrogen levels, and incidence of heart failure. CCr was calculated with adjusted body weight (AdjBW). AdjBW was selected as a predictor of the volume of distribution in the central and peripheral compartments. External validation showed that the highest proportion of cases had deviations of less than 15 % between measured and predicted values in the final model developed in this study. This indicates that our model outperforms previously developed models (five for obese patients and four for non-obese patients).
CONCLUSIONS: Our model shows that determining effective vancomycin doses for overweight and obese patients depend on estimated CCr rates, AdjBW, BUN levels, and incidence of heart failure.