Pharmacokinetics and in vitro blood-brain barrier screening of the plant-derived alkaloid tryptanthrin
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Autor:innen
Jähne, Evelyn A.
Eigenmann, Daniela E.
Sampath, Chethan
Butterweck, Veronika
Culot, Maxime
Cecchelli, Roméo
Gosselet, Fabien
Walter, Fruzsina R.
Deli, Maria A.
Smiesko, Martin
Autor:in (Körperschaft)
Publikationsdatum
2016
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Planta Medica
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
82
Ausgabe / Nummer
11-12
Seiten / Dauer
1021-1029
Patentnummer
Verlag / Herausgebende Institution
Thieme
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
The indolo[2,1-b]quinazoline alkaloid tryptanthrin was previously identified as a potent anti-inflammatory compound with a unique pharmacological profile. It is a potent inhibitor of cyclooxygenase-2, 5-lipooxygenase-catalyzed leukotriene synthesis, and nitric oxide production catalyzed by the inducible nitric oxide synthase. To characterize the pharmacokinetic properties of tryptanthrin, we performed a pilot in vivo study in male Sprague-Dawley rats (2 mg/kg bw i. v.). Moreover, the ability of tryptanthrin to cross the blood-brain barrier was evaluated in three in vitro human and animal blood-brain barrier models. Bioanalytical UPLC-MS/MS methods used were validated according to current international guidelines. A half-life of 40.63 ± 6.66 min and a clearance of 1.00 ± 0.36 L/h/kg were found in the in vivo pharmacokinetic study. In vitro data obtained with the two primary animal blood-brain barrier models showed a good correlation with an immortalized human monoculture blood-brain barrier model (hBMEC cell line), and were indicative of a high blood-brain barrier permeation potential of tryptanthrin. These findings were corroborated by the in silico prediction of blood-brain barrier penetration. P-glycoprotein interaction of tryptanthrin was assessed by calculation of the efflux ratio in bidirectional permeability assays. An efflux ratio below 2 indicated that tryptanthrin is not subjected to active efflux.
Schlagwörter
tryptanthrin, UPLC-MS/MS, validation, pharmacokinetics (PK), blood-brain barrier (BBB)
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1439-0221
0032-0943
0032-0943
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
Jähne, E. A., Eigenmann, D. E., Sampath, C., Butterweck, V., Culot, M., Cecchelli, R., Gosselet, F., Walter, F. R., Deli, M. A., Smiesko, M., Hamburger, M., & Oufir, M. (2016). Pharmacokinetics and in vitro blood-brain barrier screening of the plant-derived alkaloid tryptanthrin. Planta Medica, 82(11-12), 1021–1029. https://doi.org/10.1055/s-0042-105295