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dc.creatorObradović, Darija
dc.creatorAndrić, Filip
dc.creatorZlatović, Mario
dc.creatorAgbaba, Danica
dc.date.accessioned2019-09-02T12:03:12Z
dc.date.available2019-09-02T12:03:12Z
dc.date.issued2018
dc.identifier.issn0886-9383
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3036
dc.description.abstractAripiprazole and ziprasidone are atypical antipsychotic drugs with the effect on positive and negative symptoms of schizophrenia, mania, and mixed states of bipolar disorder. Hansen's solubility parameters, (d), (p), and (h), which account for dispersive, polarizable, and hydrogen bonding contributions to the overall cohesive energy of a compound, are often used to assess pharmacokinetic properties of drugs. However, no data exist of solubility parameters for the drugs of interest in this study. Therefore, in the present study, partial least square regression (PLS), artificial neural networks (ANNs), regression trees (RT), boosted trees (BT), and random forests (RF) were applied to estimate Hansen's solubility parameters of ziprasidone, aripiprazole, and their impurities/metabolic derivatives, targeting their biopharmaceutical classes and absorption routes. A training set of 47 structurally diverse and pharmacologically active compounds and 290 molecular descriptors and pharmaceutically important properties were used to build the prediction models. The modeling approaches were compared by the sum of ranking differences, using the consensus values as a reference for the unknowns and the experimentally determined values as a gold standard for the calibration set. In both instances, the PLS models, together with ANNs, demonstrated better performance than RT, BT and especially RF. Based on the best scored models, we were able to pinpoint the most probable absorption sites for each drug and the corresponding metabolite, i.e., the upper parts of the gastrointestinal tract, small intestine, or absorption along entire length of gastrointestinal tract.en
dc.publisherWiley, Hoboken
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172033/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Chemometrics
dc.subjectartificial neural network (ANN)en
dc.subjectdrug absorptionen
dc.subjectHansen's solubility parametersen
dc.subjectpartial least square regression (PLS)en
dc.subjectsum of ranking difference (SRD)en
dc.titleModeling of Hansen's solubility parameters of aripiprazole, ziprasidone, and their impurities: A nonparametric comparison of models for prediction of drug absorption sitesen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractAгбаба, Даница; Aндрић, Филип; Обрадовић, Дарија; Златовић, Марио;
dc.citation.volume32
dc.citation.issue4
dc.citation.other32(4): -
dc.citation.rankM21
dc.identifier.wos000430668000007
dc.identifier.doi10.1002/cem.2996
dc.identifier.scopus2-s2.0-85040642229
dc.identifier.rcubconv_3958
dc.type.versionpublishedVersion


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