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dc.contributor.authorPark, Yu Mi
dc.contributor.authorMeyer, Markus R
dc.contributor.authorMüller, Rolf
dc.contributor.authorHerrmann, Jennifer
dc.date.accessioned2020-10-26T10:38:58Z
dc.date.available2020-10-26T10:38:58Z
dc.date.issued2020-09-29
dc.identifier.citationMolecules. 2020 Sep 29;25(19):E4474. doi: 10.3390/molecules25194474.en_US
dc.identifier.pmid33003405
dc.identifier.doi10.3390/molecules25194474
dc.identifier.urihttp://hdl.handle.net/10033/622534
dc.description.abstractZebrafish (Danio rerio) larvae have gained attention as a valid model to study in vivo drug metabolism and to predict human metabolism. The microinjection of compounds, oligonucleotides, or pathogens into zebrafish embryos at an early developmental stage is a well-established technique. Here, we investigated the metabolism of zebrafish larvae after microinjection of methyl 2-(1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamido)-3,3-dimethylbutanoate (7'N-5F-ADB) as a representative of recently introduced synthetic cannabinoids. Results were compared to human urine data and data from the in vitro HepaRG model and the metabolic pathway of 7'N-5F-ADB were reconstructed. Out of 27 metabolites detected in human urine samples, 19 and 15 metabolites were present in zebrafish larvae and HepaRG cells, respectively. The route of administration to zebrafish larvae had a major impact and we found a high number of metabolites when 7'N-5F-ADB was microinjected into the caudal vein, heart ventricle, or hindbrain. We further studied the spatial distribution of the parent compound and its metabolites by mass spectrometry imaging (MSI) of treated zebrafish larvae to demonstrate the discrepancy in metabolite profiles among larvae exposed through different administration routes. In conclusion, zebrafish larvae represent a superb model for studying drug metabolism, and when combined with MSI, the optimal administration route can be determined based on in vivo drug distribution.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject3R principleen_US
dc.subjectHepaRG cellsen_US
dc.subjectadministration routeen_US
dc.subjectdrug metabolism and pharmacokinetics (DMPK)en_US
dc.subjectmass spectrometry imaging (MSI)en_US
dc.subjectmetabolismen_US
dc.subjectmethyl 2-(1-(5-fluoropentyl)-1H-pyrrolo [2,3-b]pyridine-3-carboxamido)-3,3-dimethylbutanoate (7′N-5F-ADB)en_US
dc.subjectmicroinjectionen_US
dc.subjectsynthetic cannabinoiden_US
dc.subjectzebrafish larvae modelen_US
dc.titleDrug Administration Routes Impact the Metabolism of a Synthetic Cannabinoid in the Zebrafish Larvae Model.en_US
dc.typeArticleen_US
dc.identifier.eissn1420-3049
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalMolecules (Basel, Switzerland)en_US
dc.source.volume25
dc.source.issue19
refterms.dateFOA2020-10-26T10:38:59Z
dc.source.journaltitleMolecules (Basel, Switzerland)
dc.source.countrySwitzerland


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