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Use of the Distribution Coefficient in Brain Polar Lipids for the Assessment of Drug-Induced Phospholipidosis Risk
- Publication Year :
- 2017
-
Abstract
- In vitro safety assessment in early drug discovery represents an important step to detect potential safety-related liabilities. It reduces late stage attrition and allows candidate optimization. In this study, we report on the use of the LogDBPL assay (a recently published assay for the determination of drug distribution coefficients between an aqueous phase and porcine brain polar lipids extract) for phospholipidosis (PLD) risk evaluation. The LogDBPL parameter was first compared to the effective permeability in the parallel artificial membrane permeability assay (PAMPA), previously reported as correlating with PLD risk. Subsequently, the LogDBPL for a set of 234 drugs with known PLD effect was measured, representing the largest data set of LogDBPL data published so far, and the correlation with phospholipid accumulation was further investigated. In addition, a comparison with other in silico methods based on physicochemical parameters is reported. Results showed that LogDBPL is an efficient descriptor t...
- Subjects :
- 0301 basic medicine
in silico methods
Drug-Related Side Effects and Adverse Reactions
Swine
In silico
Phospholipid
Synthetic membrane
Analytical chemistry
Toxicology
Lipidoses
030226 pharmacology & pharmacy
drugs
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
brain polar lipids
Animals
distribution coefficients
Phospholipids
Phospholipidosis
Principal Component Analysis
Chromatography
Chemistry
Drug discovery
phospholipidosis, distribution coefficients, brain polar lipids, drugs, permeability, in silico methods
Brain
General Medicine
phospholipidosis
Partition coefficient
030104 developmental biology
Pharmaceutical Preparations
Permeability (electromagnetism)
lipids (amino acids, peptides, and proteins)
permeability
Relative permeability
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....85a3a36dac676bf240b7f1b7fa63f851