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Journal of pharmaceutical health care and sciences
Mar 12, 2025;11 (1): 18.

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

Keisuke Takada, Masaru Samura, Yuki Igarashi, Ayako Suzuki, Tomoyuki Ishigo, Satoshi Fujii, Yuta Ibe, Hiroaki Yoshida, Hiroaki Tanaka, Fumiya Ebihara, Takumi Maruyama, Yukihiro Hamada, Toshiaki Komatsu, Atsushi Tomizawa, Akitoshi Takuma, Hiroaki Chiba, Yusuke Yagi, Yoshifumi Nishi, Yuki Enoki, Kazuaki Taguchi, Koji Tanikawa, Hiroyuki Kunishima, Kazuaki Matsumoto
Author Information
  1. Keisuke Takada: Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-Ku, Tokyo, 105-8512, Japan.
  2. Masaru Samura: Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-Ku, Tokyo, 105-8512, Japan. masaru.samura@gmail.com.
  3. Yuki Igarashi: Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-Ku, Tokyo, 105-8512, Japan.
  4. Ayako Suzuki: Department of Pharmacy, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-Ku, Yokohama-Shi, Kanagawa, 227-8501, Japan.
  5. Tomoyuki Ishigo: Department of Pharmacy, Sapporo Medical University Hospital, 291 Nishi 16-Chome, Minami 1-Jo, Chuo-Ku, Sapporo-Shi, Hokkaido, 060-8543, Japan.
  6. Satoshi Fujii: Department of Pharmacy, Sapporo Medical University Hospital, 291 Nishi 16-Chome, Minami 1-Jo, Chuo-Ku, Sapporo-Shi, Hokkaido, 060-8543, Japan.
  7. Yuta Ibe: Department of Pharmacy, Sapporo Medical University Hospital, 291 Nishi 16-Chome, Minami 1-Jo, Chuo-Ku, Sapporo-Shi, Hokkaido, 060-8543, Japan.
  8. Hiroaki Yoshida: Department of Pharmacy, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611, Japan.
  9. Hiroaki Tanaka: Department of Pharmacy, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611, Japan.
  10. Fumiya Ebihara: Department of Pharmacy, Tokyo Women's Medical University Hospital, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan.
  11. Takumi Maruyama: Department of Pharmacy, Tokyo Women's Medical University Hospital, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan.
  12. Yukihiro Hamada: Department of Pharmacy, Kochi Medical School Hospital, 185-1 Okochokohasu, Nankoku-Shi, Kochi, 783-8505, Japan.
  13. Toshiaki Komatsu: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara-Shi, Kanagawa, 252-0375, Japan.
  14. Atsushi Tomizawa: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara-Shi, Kanagawa, 252-0375, Japan.
  15. Akitoshi Takuma: Department of Pharmacy, Showa University Northern Yokohama Hospital, 35-1 Chigasaki-Chuo, Tsuzuki-Ku, Yokohama-Shi, Kanagawa, 224-0032, Japan.
  16. Hiroaki Chiba: Department of Pharmacy, Tohoku Kosai Hospital, 2-3-11 Kokubuncho, Aoba-Ku, Sendai-Shi, Miyagi, 980-0803, Japan.
  17. Yusuke Yagi: Department of Pharmacy, Kochi Medical School Hospital, 185-1 Okochokohasu, Nankoku-Shi, Kochi, 783-8505, Japan.
  18. Yoshifumi Nishi: Center for Pharmacist Education, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-Shi, Chiba, 274-0063, Japan.
  19. Yuki Enoki: Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-Ku, Tokyo, 105-8512, Japan.
  20. Kazuaki Taguchi: Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-Ku, Tokyo, 105-8512, Japan.
  21. Koji Tanikawa: Department of Pharmacy, Yokohama General Hospital, 2201-5 Kuroganecho, Aoba-Ku, Yokohama City, Kanagawa, 225-0025, Japan.
  22. Hiroyuki Kunishima: Department of Infectious Diseases, St. Marianna University School of Medicine Hospital, 2-16-1 Sugao, Miyamae-Ku, Kawasaki City, Kanagawa, 216-8511, Japan.
  23. Kazuaki Matsumoto: Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-Ku, Tokyo, 105-8512, Japan.
PMID: 40075546 DOI: 10.1186/s40780-025-00423-8

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)�����������(Serum albumin (Alb) /2.3)�����������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), respectively), the final model demonstrated the smallest MAE of 0.60 L/h and MSE of 0.65 (L/h) 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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Journal Article

Word Cloud

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