Development of machine learning-based quantitative structure-activity relationship models for predicting plasma...

Plasma half-life is a crucial pharmacokinetic parameter for estimating extralabel withdrawal intervals of drugs to ensure the safety of food products derived from animals. This study focuses on developing a quantitative structure-activity relationship (QSAR) model incorporating multiple machine learning and artificial intelligence algorithms, and aims to predict the plasma half-lives of drugs in 6 food animals, including cattle, chickens, goats, sheep, swine, and turkeys. By integrating 4 machine learning algorithms with 5 molecular descriptor types, 20 QSAR models were developed using data from the Food Animal Residue Avoidance Databank (FARAD) Comparative Pharmacokinetic Database. The deep neural network (DNN) algorithm demonstrated the best prediction ability of plasma half-lives. The DNN model with all descriptors achieved superior performance with a high coefficient of determination (R2) of 0.82 ± 0.19 in 5-fold cross-validation on the training sets and an R2 of 0.67 on the independent test set, indicating accurate predictions and good generalizability. The final model was converted to a user-friendly web dashboard to facilitate its wide application by the scientific community. This machine learning-based QSAR model serves as a valuable tool for predicting drug plasma half-lives and extralabel withdrawal intervals in 6 common food animals based on physicochemical properties. It also provides a foundation to develop more advanced models to predict the tissue half-life of drugs in food animals.