Jähne, Evelyn A.Eigenmann, Daniela E.Sampath, ChethanButterweck, VeronikaCulot, MaximeCecchelli, RoméoGosselet, FabienWalter, Fruzsina R.Deli, Maria A.Smiesko, MartinHamburger, MatthiasOufir, Mouhssin2016-12-132016-12-1320161439-02210032-094310.1055/s-0042-105295http://hdl.handle.net/11654/23688The 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.entryptanthrinUPLC-MS/MSvalidationpharmacokinetics (PK)blood-brain barrier (BBB)01A - Beitrag in wissenschaftlicher Zeitschrift1021-1029