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. 2025 Mar 12;11(1):18.
doi: 10.1186/s40780-025-00423-8.

Development and validation of a population pharmacokinetic model of vancomycin for patients of advanced age

Keisuke Takada  1   2 , Masaru Samura  3   4   5 , Yuki Igarashi  1   2 , Ayako Suzuki  6   7 , Tomoyuki Ishigo  8 , Satoshi Fujii  8 , Yuta Ibe  8 , Hiroaki Yoshida  9 , Hiroaki Tanaka  9 , Fumiya Ebihara  10 , Takumi Maruyama  10 , Yukihiro Hamada  11 , Toshiaki Komatsu  12 , Atsushi Tomizawa  12 , Akitoshi Takuma  13   14 , Hiroaki Chiba  15 , Yusuke Yagi  11 , Yoshifumi Nishi  16 , Yuki Enoki  1 , Kazuaki Taguchi  1 , Koji Tanikawa  2 , Hiroyuki Kunishima  17 , Kazuaki Matsumoto  1
Affiliations

Development and validation of a population pharmacokinetic model of vancomycin for patients of advanced age

Keisuke Takada et al. J Pharm Health Care Sci. .

Abstract

Background: Population pharmacokinetic (PPK) models of vancomycin (VCM) commonly use creatinine clearance (CLcr) as a covariate for clearance (CL). However, relying on CLcr in patients of advanced age may lead to inaccuracies in estimating VCM clearance. Therefore, this study aimed to develop and validate a new PPK model specifically for patients aged 75 years and older.

Methods: PPK analysis was performed based on the blood concentrations of VCM (n = 159 patients). The predictive performance of the developed model was compared with that of previous models using mean absolute error (MAE) and mean squared error (MSE) for another dataset.

Results: The PPK analysis optimized a two-compartment model using CLcr and the Alb levels as covariates at the central compartment of VCM clearance. The final model was as follows: CL (L/h) = 1.96 × (CLcr/3.09) 0.63 × (Serum albumin (Alb) /2.3) 0.22 × exponential (0.11). Clearance between the central and peripheral compartments (L/h) = 4.86. Central compartment volume of distribution (L) = 31.78. Peripheral compartment volume of distribution (L) = 53.64. The validation study revealed that compared with those of previous models (ranging from 0.67 to 0.79 L/h and from 0.81 to 1.11 (L/h)2, respectively), the final model demonstrated the smallest MAE of 0.60 L/h and MSE of 0.65 (L/h)2 for patients of advanced age with serum creatinine levels of < 0.6 mg/dL.

Conclusion: The PPK model of VCM for patients of advanced age was optimized by adding the Alb levels and CLcr as covariates for CL. The predictive accuracy of the PPK model for patients with an SCr of < 0.6 mg/dL tended to be higher than those of previous models based just on CLcr. Thus, dosage is suggested to be adjusted based on CLcr and Alb levels for patients with an SCr of < 0.6 mg/dL.

Keywords: Patients of advanced age; Population pharmacokinetics; Serum albumin; Vancomycin.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Yokohama General Hospital Ethics Committee (approval number: 2024–026) for population pharmacokinetic analysis, and by Showa University Ethics Committee for validation of the PPK model (approval number: 22–284-A). Comprehensive informed consent was obtained from the participants by displaying an opt-out option on our website. Consent for publication: Not applicable. Competing interests: HK received speaker honoraria from Shionogi Pharma Co., Ltd. KM received grant support funding from Meiji Seika Pharma Co., Ltd., and Sumitomo Pharma Co., Ltd., and speaker honoraria from Meiji Seika Pharma Co., Ltd. The other authors declare no conflicts of interests.

Figures

Fig. 1
Fig. 1
Visual predictive check plot of vancomycin. Visual predictive check plot of the vancomycin concentration versus time for the covariate model. Concentration vs. Time after dosing. Observed vs. individual predicted concentrations
Fig. 2
Fig. 2
Validation of the final model. A and B. The height of the bars indicates the mean absolute prediction error (MAE) of CL and the dosage at 250 mg intervals achieving an area under the concentration–time curve at a steady state of 500, respectively. C and D. The height of the bars indicates the mean squared error (MSE) of CL and the dosage at 250 mg intervals achieving an area under the concentration–time curve at a steady state of 500, respectively. The grey and black bars represent patients aged ≥ 75 years and patients aged ≥ 75 years with an SCr of < 0.6 mg/dL, respectively. The error bars represent their corresponding 95% confidence intervals
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