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, Evelyn A., Daniela E. EIGENMANN, Chethan SAMPATH, Veronika BUTTERWECK, Maxime CULOT, Roméo CECCHELLI, Fabien GOSSELET, Fruzsina R. WALTER, Maria A. DELI, Martin SMIESKO, Matthias HAMBURGER und Mouhssin OUFIR, 2016. Pharmacokinetics and in vitro blood-brain barrier screening of the plant-derived alkaloid tryptanthrin. Planta Medica. 2016. Bd. 82, Nr. 11-12, S. 1021–1029. DOI 10.1055/s-0042-105295. Verfügbar unter: http://hdl.handle.net/11654/23688