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AI-Driven Tacrolimus Dosing in Transplant Care: Cohort Study.

作者信息

Huo Mingjia, Perez Sean, Awdishu Linda, Kerr Janice S, Xie Pengtao, Khan Adnan, Mekeel Kristin, Nemati Shamim

机构信息

Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, United States.

Department of Surgery, University of California San Diego, La Jolla, CA, United States.

出版信息

JMIR AI. 2025 Sep 2;4:e67302. doi: 10.2196/67302.


DOI:10.2196/67302
PMID:40893105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12404564/
Abstract

BACKGROUND: Tacrolimus forms the backbone of immunosuppressive therapy in solid organ transplantation, requiring precise dosing due to its narrow therapeutic range. Maintaining therapeutic tacrolimus levels in the postoperative period is challenging due to diverse patient characteristics, donor organ factors, drug interactions, and evolving perioperative physiology. OBJECTIVE: The aim of this study is to design a machine learning model to predict the next-day tacrolimus trough concentrations (C0) and guide dosing to prevent persistent under- or overdosing. METHODS: We used retrospective data from 1597 adult recipients of kidney and liver transplants at UC San Diego Health to develop a long short-term memory (LSTM) model to predict next-day tacrolimus C0 in an inpatient setting. Predictors included transplant type, demographics, comorbidities, vital signs, laboratory parameters, ordered diet, and medications. Permutation feature importance was evaluated for the model. We further implemented a classification task to evaluate the model's ability to identify underdosing, therapeutic dosing, and overdosing. Finally, we generated next-day dose recommendations that would achieve tacrolimus C0 within the target ranges. RESULTS: The LSTM model provided a mean absolute error of 1.880 ng/mL when predicting next-day tacrolimus C0. Top predictive features included the recent tacrolimus C0, tacrolimus doses, transplant organ type, diet, and interactive drugs. When predicting underdosing, therapeutic dosing, and overdosing using a 3-class classification task, the model achieved a microaverage F1-score of 0.653. For dose recommendations, the best clinical outcomes were achieved when the actual total daily dose closely aligned with the model's recommended dose (within 3 mg). CONCLUSIONS: Ours is one of the largest studies to apply artificial intelligence to tacrolimus dosing, and our LSTM model effectively predicts tacrolimus C0 and could potentially guide accurate dose recommendations. Further prospective studies are needed to evaluate the model's performance in real-world dose adjustments.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa8/12404564/142c1e30dbc9/ai-v4-e67302-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa8/12404564/53af2d63e88a/ai-v4-e67302-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa8/12404564/83dc5a93b14e/ai-v4-e67302-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa8/12404564/142c1e30dbc9/ai-v4-e67302-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa8/12404564/53af2d63e88a/ai-v4-e67302-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa8/12404564/83dc5a93b14e/ai-v4-e67302-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa8/12404564/142c1e30dbc9/ai-v4-e67302-g003.jpg

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本文引用的文献

[1]
A critical assessment of using ChatGPT for extracting structured data from clinical notes.

NPJ Digit Med. 2024-5-1

[2]
Adapted large language models can outperform medical experts in clinical text summarization.

Nat Med. 2024-4

[3]
Long Short-term Memory-Based Prediction of the Spread of Influenza-Like Illness Leveraging Surveillance, Weather, and Twitter Data: Model Development and Validation.

J Med Internet Res. 2023-2-6

[4]
Can the Area Under the Curve/Trough Level Ratio Be Used to Optimize Tacrolimus Individual Dose Adjustment?

Transplantation. 2023-1-1

[5]
Controversial Interactions of Tacrolimus with Dietary Supplements, Herbs and Food.

Pharmaceutics. 2022-10-10

[6]
A Prediction Model for Tacrolimus Daily Dose in Kidney Transplant Recipients With Machine Learning and Deep Learning Techniques.

Front Med (Lausanne). 2022-5-27

[7]
Predicting model-informed precision dosing: A test-case in tacrolimus dose adaptation for kidney transplant recipients.

CPT Pharmacometrics Syst Pharmacol. 2022-3

[8]
All Models are Wrong, but are Useful: Learning a Variable's Importance by Studying an Entire Class of Prediction Models Simultaneously.

J Mach Learn Res. 2019

[9]
An Integrated Clinical and Genetic Prediction Model for Tacrolimus Levels in Pediatric Solid Organ Transplant Recipients.

Transplantation. 2022-3-1

[10]
Tacrolimus Exposure Prediction Using Machine Learning.

Clin Pharmacol Ther. 2021-8

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