Figure 5.

In vivo P-glycoprotein inhibition increases bumped kinase inhibitor 1318 (BKI1318) gastrointestinal concentrations. Elacridar (15 mg/kg) or vehicle control were administered to mice 15 minutes before delivery of a single oral dose of BKI1318 (30 mg/kg). Gastrointestinal tissue specimens were collected 0.5, 1, 2, 8, and 12 hours after BKI1318 dosing, and the lumen of the tissue was flushed extensively. A–C, Tissue concentrations of BKI1318 were quantified, and elacridar coadministration significantly increased the BKI1318 area under the curve in the duodenum (P < .001; A), jejunum (P < .05; B), and ileum (P < .05; C). D, However, elacridar did not generate a significant difference in the BKI1318 exposure in the cecum/colon. Each point represents the average gastrointestinal concentration (±standard deviation) observed in 3 mice. An unpaired Student t test was used to determine significance, using a significance level of 0.05.