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Titel: Are pigs a suitable animal model for in vivo metabolism studies of new psychoactive substances? A comparison study using different in vitro/in vivo tools and U-47700 as model drug
VerfasserIn: Nordmeier, Frederike
Doerr, Adrian
Laschke, Matthias W.
Menger, Michael D.
Schmidt, Peter H.
Schaefer, Nadine
Meyer, Markus R.
Sprache: Englisch
Titel: Toxicology Letters
Bandnummer: 329
Seiten: 12-19
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2020
Freie Schlagwörter: New synthetic opioids
U-47700
Pigs
Urinary metabolic patterns
LC-HR-MS/MS
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Being highly potent, New Synthetic Opioids (NSO) have become a public health concern. Little is known though about the metabolism and toxicokinetics (TK) of many of the non fentanyl NSO such as U-47700. Obtaining such data in humans is challenging and so we investigated if pigs were a suitable model species as TK model for U47700. The metabolic fate of U-47700 was elucidated after intravenous administration to one pig in vivo and results were compared to metabolic patterns formed by different other in vitro systems (human and pig liver microsomes, human liver S9 fraction) and compared to rat and human in vivo data. Furthermore, monooxygenase isozymes responsible for the major metabolic steps were elucidated. In total, 12 phase I and 8 phase II metabolites of U-47700 could be identified. The predominant reactions were N-demethylation, hydroxylation, and combination of them followed by glucuronidation or sulfation. The most predominant monooxygenase catalyzed conversions were N-demethylation, and hydroxylation by CYP3A4 and 2B6, and FMO3 catalyzed N-oxidation. Similar main phase I metabolites were found in vitro as compared to in vivo (pig/human). The metabolic pattern elucidated in the pig was comparable to human in vivo data. Thus, pigs seem to be a suitable animal model for metabolism and further TK of U-47700.
DOI der Erstveröffentlichung: 10.1016/j.toxlet.2020.04.001
URL der Erstveröffentlichung: https://doi.org/10.1016/j.toxlet.2020.04.001
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-441340
hdl:20.500.11880/39466
http://dx.doi.org/10.22028/D291-44134
ISSN: 0378-4274
Datum des Eintrags: 24-Jan-2025
Bezeichnung des in Beziehung stehenden Objekts: Supplementary data
In Beziehung stehendes Objekt: https://ars.els-cdn.com/content/image/1-s2.0-S0378427420301090-mmc2.docx
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Chirurgie
M - Experimentelle und Klinische Pharmakologie und Toxikologie
M - Rechtsmedizin
Professur: M - Prof. Dr. Michael D. Menger
M - Prof. Dr. Markus Meyer
M - Prof. Dr. Peter Schmidt
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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