Publikation:
Development of a multi-compartment pharmacokinetic model to characterize the exposure to Hexamoll® DINCH®

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dc.contributor.authorSchütze, Andre
dc.contributor.authorApel, Petra
dc.contributor.authorLorber, Matthew
dc.contributor.authorGawrych, Katarzyna
dc.contributor.authorKolossa-Gehring, Marike
dc.contributor.authorBrüning, Thomas
dc.contributor.authorKoch, Holger Martin
dc.date.accessioned2024-06-16T16:16:51Z
dc.date.available2024-06-16T16:16:51Z
dc.date.issued2015
dc.description.abstractWe developed and calibrated a multi compartment pharmacokinetic (PK) model to predict urinary concentrations after oral exposure of four specific DINCH metabolites: MINCH, OH-MINCH, cx-MINCH, and oxo-MINCH. This descriptive model has 4 compartments: a "stomachŁ (SC) compartment, a "holdingŁ (HC) compartment, a "bloodŁ (BC) compartment and a "bladderŁ (BLC) compartment. DINCH is assumed to first deposit into the SC, with transfer split between the HC and the BC. Unmetabolized DINCH from the HC then transfers to the BC. The DINCH metabolism is assumed to occur in the BC before excretion via the BLC. At each urination event, all the metabolite mass in the BLC is excreted. The model was calibrated using published urine metabolite data from 3 different male volunteers, each orally dosed with 50 mg DINCH. Full urine voids were taken for 48 h after dosage. The predicted values showed a good agreement with the observed urinary DINCH metabolite concentrations, with a Spearman correlation coefficient exceeding 0.7 for all oxidized metabolites. We showed the importance of a holding reservoir. Without it, a good agreement could not be found. We applied the model to a set of 24-h general population samples measured for DINCH metabolites. The model was unable to duplicate the ratio of metabolites seen in the 24-h samples. Two possibilities were offered to explain the difference: the exposure pattern in the general population did not match the oral exposure in the dosing experiments, or the long-term toxicokinetics of DINCH was not captured in the 48-h controlled dosing experiments.Quelle: http://www.sciencedirect.comen
dc.identifier.doihttps://doi.org/10.60810/openumwelt-1251
dc.identifier.urihttps://openumwelt.de/handle/123456789/8295
dc.language.isoeng
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectDINCH
dc.subjectExpositionsabschätzung
dc.titleDevelopment of a multi-compartment pharmacokinetic model to characterize the exposure to Hexamoll® DINCH®
dc.typeWissenschaftlicher Artikel
dspace.entity.typePublication
local.bibliographicCitation.journalTitleChemosphere
local.bibliographicCitation.originalDOI10.1016/j.chemosphere.2015.01.056
local.bibliographicCitation.volume128 (2015), Seite 216-224
local.collectionAufsätze
local.contributor.authorId02157262
local.contributor.authorId00380361
local.contributor.authorId02168276
local.contributor.authorId00415753
local.contributor.authorId02110258
local.identifier.catalogId02418341
local.ingest.leader05443naa a2200000uu 4500
local.jointTitleDEVELOPMENT OF A MULTICOMPARTMENT PHARMACOKINETIC MODEL TO CHARACTERIZE THE EXPOSURE TO HEXAMOLL DINCH
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local.source.urihttp://Webde/gruppen/bibliothek/Einzelaufsaetze/Einzelaufsaetze-EA/EA004171.pdf
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