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Machine Learning predicts the effect of food on orally administered medicines

Gavins, FKH; Fu, Z; Elbadawi, M; Basit, AW; Rodrigues, MRD; Orlu, M; (2022) Machine Learning predicts the effect of food on orally administered medicines. International Journal of Pharmaceutics , 611 , Article 121329. 10.1016/j.ijpharm.2021.121329. (In press).

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Abstract

Food-mediated changes to drug absorption, termed the food effect, are hard to predict and can have significant implications for the safety and efficacy of oral drug products in patients. Mimicking the prandial states of the human gastrointestinal tract in preclinical studies is challenging, poorly predictive and can produce difficult to interpret datasets. Machine learning (ML) has emerged from the computer science field and shows promise in interpreting complex datasets present in the pharmaceutical field. A ML-based approach aimed to predict the food effect based on an extensive dataset of over 311 drugs with more than 20 drug physicochemical properties, referred to as features. Machine learning techniques were tested; including logistic regression, support vector machine, k-Nearest neighbours and random forest. First a standard ML pipeline using a 80:20 split for training and testing was tried to predict no food effect (F0), negative food effect (F-) and positive food effect (F+), however this lead to specificities of less than 40%. To overcome this, a strategic ML pipeline was devised and three tasks were developed. Random forest achieved the strongest performance overall. High accuracies and sensitivities of 70%, 80% and 70% and specificities of 71%, 76% and 71% were achieved for classifying; (i) no food effect vs food effect, (ii) negative food vs positive food effect and (iii) no food effect vs negative food effect vs positive food effect, respectively. Feature importance using random forest ranked the features by importance for building the predictive tasks. The calculated dose number was the most important feature. Here, ML has provided an effective screening tool for predicting the food effect, with the potential to select lead compounds with no food effect, reduce the number of animal studies, and accelerate oral drug development studies.

Type: Article
Title: Machine Learning predicts the effect of food on orally administered medicines
Location: Netherlands
DOI: 10.1016/j.ijpharm.2021.121329
Publisher version: http://dx.doi.org/10.1016/j.ijpharm.2021.121329
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: biopharmaceutics, computational pharmaceutics, computational screening and prediction, digital pharmaceutics, drug products, machine learning, permeability, personalisation, pharmacokinetics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10139617
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