Predicting Bile and Lipid Interaction for Drug Substances.
Mol Pharm
; 19(8): 2868-2876, 2022 08 01.
Article
em En
| MEDLINE
| ID: mdl-35776440
ABSTRACT
Predicting biopharmaceutical characteristics and food effects for drug substances may substantially leverage rational formulation outcomes. We established a bile and lipid interaction prediction model for new drug substances and further explored the model for the prediction of bile-related food effects. One hundred and forty-one drugs were categorized as bile and/or lipid interacting and noninteracting drugs using 1H nuclear magnetic resonance (NMR) spectroscopy. Quantitative structure-property relationship modeling with molecular descriptors was applied to predict a drug's interaction with bile and/or lipids. Bile interaction, for example, was indicated by two descriptors characterizing polarity and lipophilicity with a high balanced accuracy of 0.8. Furthermore, the predicted bile interaction correlated with a positive food effect. Reliable prediction of drug substance interaction with lipids required four molecular descriptors with a balanced accuracy of 0.7. These described a drug's shape, lipophilicity, aromaticity, and hydrogen bond acceptor capability. In conclusion, reliable models might be found through drug libraries characterized for bile interaction by NMR. Furthermore, there is potential for predicting bile-related positive food effects.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bile
/
Relação Quantitativa Estrutura-Atividade
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article