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RESEARCH PRODUCT
A topological sub-structural approach for predicting human intestinal absorption of drugs.
Liliana Ramos TorresMarival Bermejo SanzMaykel Pérez GonzálezRicardo Grau ÁValosHumberto González DíazMiguel ÁNgel Cabrera Pérezsubject
PharmacologyQuantitative structure–activity relationshipChemistryOrganic ChemistryBiological AvailabilityQuantitative Structure-Activity RelationshipGeneral MedicineModels TheoreticalLinear discriminant analysisTopologyCross-validationIntestinal absorptionBioavailabilityIntestinal AbsorptionPharmaceutical PreparationsTest setDrug DiscoveryHuman intestinal absorptionCutoffHumansIntestinal Mucosadescription
The human intestinal absorption (HIA) of drugs was studied using a topological sub-structural approach (TOPS-MODE). The drugs were divided into three classes according to reported cutoff values for HIA. "Poor" absorption was defined as HIAor =30%, "high" absorption as HIAor =80%, whereas "moderate" absorption was defined between these two values (30%HIA79%). Two linear discriminant analyses were carried out on a training set of 82 compounds. The percentages of correct classification, for both models, were 89.02%. The predictive power of the models were validated by three test: a leave-one-out cross validation procedure (88.9% and 87.9%), an external prediction set of 127 drugs (92.9% and 80.31%) and a test set of 109 oral drugs with bioavailability values reported (93.58% and 91.84%). Finally, positive and negative sub-structural contributions to the HIA were identified and their possibilities in the lead generation and optimization process were evaluated.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2004-01-12 | European journal of medicinal chemistry |