Sascha Freiwald

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Axitinib is an inhibitor of tyrosine kinase vascular endothelin growth factor receptors 1, 2, and 3. The ATP-binding cassette (ABC) and solute carrier (SLC) transport properties of axitinib were determined in selected cellular systems. Axitinib exhibited high passive permeability in all cell lines evaluated (Papp ≥ 6 × 10(-6) cm/s). Active efflux was(More)
Several antihistamine drugs including terfenadine, ebastine, and astemizole have been identified as substrates for CYP2J2. The overall importance of this enzyme in drug metabolism has not been fully explored. In this study, 139 marketed therapeutic agents and compounds were screened as potential CYP2J2 substrates. Eight novel substrates were identified that(More)
CYP2J2, an arachidonic acid epoxygenase, is recognized for its role in the first-pass metabolism of astemizole and ebastine. To fully assess the role of CYP2J2 in drug metabolism, a selective substrate and potent specific chemical inhibitor are essential. In this study, we report amiodarone 4-hydoxylation as a specific CYP2J2-catalyzed reaction with no(More)
PK express module is a physiologically based model of first pass metabolism, which integrates in vitro data with an in silico physiologically based pharmacokinetic (PBPK) model to predict human bioavailability (F(H)). There are three required inputs: FDp (Fraction dose absorbed, final parameter from iDEA absorption module), protein binding (fu) and(More)
An automated high throughput human hepatocyte assay has been established with a 96-well format using a Tecan Genesistrade mark Workstation. Validation of this assay was performed with nine commercially available compounds and an additional 10 Pfizer compounds with varying hepatic extraction ratios (E(H)) ranging from 0.02 to approximately 1. The incubation(More)
An interactive computer graphic system has been developed for 3-D reconstruction of stained serial sections. The system has been used for 3-D reconstruction of portions of mouse lung containing melanoma nodules. A stereoscopic color picture of a wire model of the reconstructed object is produced. The volume, surface area, and sphericity index of structures(More)
N-Methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide (axitinib) is an oral inhibitor of vascular endothelial growth factor receptors 1-3, which is approved for the treatment of advanced renal cell cancer. Human [(14)C]-labeled clinical studies indicate axitinib's primary route of clearance is metabolism. The aims of the in vitro(More)
Axitinib is an inhibitor of tyrosine kinase vascular endothelin growth factor receptors 1-3. ABC and SLC transport properties of axitinib were determined in selected cellular systems. Axitinib exhibited high passive permeability in all cell lines evaluated (Papp ≥ 6 x 10-6 cm/sec). Active efflux was observed in Caco-2 cells and further evaluation in MDR1-or(More)