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基于模型的替考拉宁精准给药以快速达到浓度-时间曲线下目标面积:一项模拟研究。

Model-informed precision dosing of teicoplanin for the rapid achievement of the target area under the concentration-time curve: A simulation study.

机构信息

Department of Pharmacy, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.

Department of Infection Control, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan.

出版信息

Clin Transl Sci. 2023 Apr;16(4):704-713. doi: 10.1111/cts.13484. Epub 2023 Feb 7.

Abstract

Teicoplanin, a glycopeptide antimicrobial, is recommended for therapeutic drug monitoring, but it remains unclear how to target the area under the concentration-time curve (AUC). This simulation study purposed to demonstrate the potential of the Bayesian forecasting approach for the rapid achievement of the target AUC for teicoplanin. We generated concordant and discordant virtual populations against a Japanese population pharmacokinetic model. The predictive performance of the Bayesian posterior AUC in limited sampling on the first day against the reference AUC was evaluated as an acceptable target AUC ratio within the range of 0.8-1.2. In the concordant population, the probability for the maximum a priori or Bayesian posterior AUC on the first day (AUC ) was 61.3% or more than 77.0%, respectively. The Bayesian posterior AUC on the second day (AUC ) was more than 75.1%. In the discordant population, the probability for the maximum a priori or Bayesian posterior AUC was 15.5% or 11.7-80.7%, respectively. The probability for the maximum a priori or Bayesian posterior AUC was 23.4%, 30.2-82.1%. The AUC at steady-state (AUC ) was correlated with trough concentration at steady-state, with a coefficient of determination of 0.930; the coefficients on days 7 and 4 were 0.442 and 0.125, respectively. In conclusion, this study demonstrated that early sampling could improve the probability of AUC and AUC but did not adequately predict AUC . Further studies are necessary to apply early sampling-based model-informed precision dosing in the clinical settings.

摘要

替考拉宁是一种糖肽类抗菌药物,推荐进行治疗药物监测,但如何确定浓度-时间曲线下面积(AUC)的目标值仍不清楚。本模拟研究旨在展示贝叶斯预测方法在快速达到替考拉宁目标 AUC 方面的潜力。我们针对日本人群药代动力学模型生成了一致和不一致的虚拟人群。在第 1 天进行有限采样时,贝叶斯后验 AUC 对参考 AUC 的预测性能评价为可接受的目标 AUC 比值范围在 0.8-1.2 内。在一致人群中,第 1 天最大先验或贝叶斯后验 AUC(AUC )的概率分别为 61.3%或 77.0%以上。第 2 天的贝叶斯后验 AUC(AUC )超过 75.1%。在不一致人群中,最大先验或贝叶斯后验 AUC 的概率分别为 15.5%或 11.7-80.7%。最大先验或贝叶斯后验 AUC 的概率为 23.4%、30.2-82.1%。稳态 AUC(AUC )与稳态谷浓度相关,决定系数为 0.930;第 7 天和第 4 天的系数分别为 0.442 和 0.125。综上所述,本研究表明早期采样可以提高 AUC 和 AUC 的概率,但不能充分预测 AUC 。需要进一步的研究来将基于早期采样的模型指导下的精准给药应用于临床实践中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e250/10087075/e60cedebd94b/CTS-16-704-g002.jpg

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