Kazutaka Oda1,2, Yumi Hashiguchi3, Toshimi Kimura4, Yasuhiro Tsuji5, Kensuke Shoji6, Yoshiko Takahashi7, Kazuaki Matsumoto8, Hideki Kawamura9, Hideyuki Saito3, Yoshio Takesue10. 1. Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto, 860-8556, Japan. kazutakaoda@kuh.kumamoto-u.ac.jp. 2. Department of Infection Control, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto, 860-8556, Japan. kazutakaoda@kuh.kumamoto-u.ac.jp. 3. Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto, 860-8556, Japan. 4. Department of Pharmacy, Tokyo Women's Medical University Hospital, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 5. Center for Pharmacist Education, School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba, 274-8555, Japan. 6. Division of Infectious Diseases, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 7. Department of Pharmacy, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya-shi, Hyogo, 663-8501, Japan. 8. Division of Pharmacodynamics, Keio University Faculty of Pharmacy, 1-5-30, Shibakoen, Minato-ku, Tokyo, 105-8512, Japan. 9. Department of Infection Control and Prevention, Kagoshima University Hospital, 8-35-1, Sakuragaoka, Kagoshima-shi, Kagoshima, 890-8520, Japan. 10. Department of Infection Control and Prevention, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya-shi, Hyogo, 663-8501, Japan.
Abstract
PURPOSE: Therapeutic drug monitoring guided by the area under the concentration-time curve (AUC-guided TDM) is recommended for vancomycin. However, validated efficient software remains elusive to popularize AUC-guided TDM in Japan. The aim of this study was to validate a newly developed web application, PAT, for AUC estimation. METHODS: PAT was developed on the R ver. 3.6.2 platform for use with mobile phones and personal computers. AUC estimated by PAT (AUCPAT) was evaluated against the reference AUC (AUCREF) calculated with the log-linear trapezoidal rule using eight measured concentrations, or against AUC (AUCBM-P) calculated using an evaluated available software with clinical data. RESULTS: Investigating the best sampling points with limited sampling, PAT produced the least bias using two concentrations at 1 h and 11 h after the end of infusion (slope 1.18, intercept -15.57, median AUCPAT/AUCREF 0.93 [range 0.81-1.24]), where only one estimation (6%) was out of the predetermined acceptable range of 0.8-1.2. Employment of only a trough concentration was more biased (AUCPAT/AUCREF range 0.73-1.30 for 11 h, AUCPAT/AUCREF range 0.62-1.40 for 23 h). In comparison with the evaluated software, AUCPAT was not biased against the AUCBM-P (slope 1.04, intercept -15.80, median AUCPAT/AUCBM-P 1.00 [range 0.86-1.10]). CONCLUSIONS: The new application using two concentrations was appropriately validated and might be efficient in popularizing the AUC-guided TDM of vancomycin.
PURPOSE: Therapeutic drug monitoring guided by the area under the concentration-time curve (AUC-guided TDM) is recommended for vancomycin. However, validated efficient software remains elusive to popularize AUC-guided TDM in Japan. The aim of this study was to validate a newly developed web application, PAT, for AUC estimation. METHODS: PAT was developed on the R ver. 3.6.2 platform for use with mobile phones and personal computers. AUC estimated by PAT (AUCPAT) was evaluated against the reference AUC (AUCREF) calculated with the log-linear trapezoidal rule using eight measured concentrations, or against AUC (AUCBM-P) calculated using an evaluated available software with clinical data. RESULTS: Investigating the best sampling points with limited sampling, PAT produced the least bias using two concentrations at 1 h and 11 h after the end of infusion (slope 1.18, intercept -15.57, median AUCPAT/AUCREF 0.93 [range 0.81-1.24]), where only one estimation (6%) was out of the predetermined acceptable range of 0.8-1.2. Employment of only a trough concentration was more biased (AUCPAT/AUCREF range 0.73-1.30 for 11 h, AUCPAT/AUCREF range 0.62-1.40 for 23 h). In comparison with the evaluated software, AUCPAT was not biased against the AUCBM-P (slope 1.04, intercept -15.80, median AUCPAT/AUCBM-P 1.00 [range 0.86-1.10]). CONCLUSIONS: The new application using two concentrations was appropriately validated and might be efficient in popularizing the AUC-guided TDM of vancomycin.
Entities:
Keywords:
area under the concentration-time curve; bayesian; software; therapeutic drug monitoring; vancomycin
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