Use of QSPR Modeling to Characterize In Vitro Binding of Drugs to a Gut-Restricted Polymer.
Pharm Res
; 35(4): 89, 2018 Mar 08.
Article
em En
| MEDLINE
| ID: mdl-29520505
ABSTRACT
PURPOSE:
Polymeric drugs, including patiromer (Veltassa®), bind target molecules or ions in the gut, allowing fecal elimination. Non-absorbed insoluble polymers, like patiromer, avoid common systemic drug-drug interactions (DDIs). However, the potential for DDI via polymer binding to orally administered drugs during transit of the gastrointestinal tract remains. Here we elucidate the properties correlated with drug-patiromer binding using quantitative structure-property relationship (QSPR) models.METHODS:
We selected 28 drugs to evaluate for binding to patiromer in vitro over a range of pH and ionic conditions intended to mimic the gut environment. Using this in vitro data, we developed QSPR models using step-wise linear regression and analyzed over 100 physiochemical drug descriptors.RESULTS:
Four descriptors emerged that account for ~70% of patiromer-drug binding in vitro the computed surface area of hydrogen bond accepting atoms, ionization potential, electron affinity, and lipophilicity (R 2 = 0.7, Q 2 = 0.6). Further, certain molecular properties are shared by nonbinding, weak, or strong binding compounds.CONCLUSIONS:
These findings offer insight into drivers of in vitro binding to patiromer and describe a useful approach for assessing potential drug-binding risk of investigational polymeric drugs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Relação Quantitativa Estrutura-Atividade
/
Pesquisa Farmacêutica
/
Modelos Biológicos
Tipo de estudo:
Evaluation_studies
/
Prognostic_studies
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos