Optimization of voriconazole dosage via population pharmacokinetic analysis based on the albumin-bilirubin (ALBI) score of patients with liver dysfunction

Nashimoto, Shunsuke; Sugawara, Mitsuru; Takekuma, Yoh

Optimization of voriconazole dosage via population pharmacokinetic analysis based on the albumin-bilirubin (ALBI) score of patients with liver dysfunction

Nashimoto, Shunsuke; Sugawara, Mitsuru; Takekuma, Yoh

Journal of infection and chemotherapy, 2025, 31(8), 102766

Permalink : https://hdl.handle.net/2115/97955

このアイテムのアクセス数:71件（2026-10-12 00:44 集計）

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ファイル	フォーマット	サイズ	閲覧回数	説明
VRCZ PPK JIC 3rd revised version_huscap	pdf	1.87 MB	54
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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/97955
タイトル	Optimization of voriconazole dosage via population pharmacokinetic analysis based on the albumin-bilirubin (ALBI) score of patients with liver dysfunction
著者	Nashimoto, Shunsuke ; Sugawara, Mitsuru ; Takekuma, Yoh
e-Rad_Researcher 40968525 著者名 Nashimoto, Shunsuke
e-Rad_Researcher 60332467 著者名 Sugawara, Mitsuru
e-Rad_Researcher 00396293 著者名 Takekuma, Yoh
言語	英語
キーワード	Voriconazole
	Therapeutic drug monitoring
	Population pharmacokinetic analysis
	Albumin-bilirubin (ALBI) score
発行日	2025-07-02
出版者	Elsevier
収録物名	Journal of infection and chemotherapy
巻(号)	31(8)
ページ	102766
抄録	Introduction: Voriconazole (VRCZ) is an antifungal agent used to treat refractory fungal infections. Its dosage is adjusted based on the individual liver function. In this study, we aimed to establish a population pharmacokinetic analysis model based on the albumin-bilirubin (ALBI) score to objectively assess the liver function using only albumin and total bilirubin levels as covariates. Methods: In total, 126 plasma samples of 16 patients with liver dysfunction who received oral VRCZ between 2012 and 2022 were analyzed in this study. Phoenix NLME software was used for population pharmacokinetic analysis, and Monte Carlo simulations were performed to determine the optimal dosing regimen to achieve the target blood VRCZ concentration. Results: Blood VRCZ concentration was described using a one-compartment model with lag time. In the final model, objective function was significantly decreased upon ALBI score incorporation into clearance. Monte Carlo simulations showed that the optimal dosing schedules were 100 mg twice daily, 75 mg twice daily, and 50 mg twice daily for ALBI scores of-3,-2, and-1, respectively. Notably, for an ALBI score of 0, target blood VRCZ concentration was exceeded, even a dosing regimen of 50 mg twice daily. Conclusion: To the best of our knowledge, this study is the first to incorporate the ALBI score into a population pharmacokinetic model for VRCZ. Our simulation results suggest that the maintenance dose should be reduced based on the ALBI score. Furthermore, our findings highlight the potential use of the ALBI score for optimal drug dosage design.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2025. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1341-321X
EISSN	1437-7780
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.jiac.2025.102766