Jim J Xiao, Dorota Nowak, Rodryg Ramlau, Monika Tomaszewska-Kiecana, Piotr J Wysocki, Jeff Isaacson, Jeri Beltman, Eileen Nash, Robert Kaczanowski, Gerhard Arold, Simon Watkins
This phase 1 study (CO-338-044; NCT02740712), conducted in patients with an advanced solid tumor, evaluated the effect of the poly(ADP-ribose) polymerase inhibitor rucaparib on the pharmacokinetics of caffeine 200 mg, warfarin 10 mg, omeprazole 40 mg, and midazolam 2 mg (cytochrome P450 [CYP] 1A2, CYP2C9, CYP2C19, and CYP3A substrates; dosed as a cocktail) and digoxin 0.25 mg (P-glycoprotein substrate; dosed separately) without rucaparib and following oral rucaparib 600 mg twice daily (BID). Geometric mean (GM) ratios (90% CI) of AUC from time zero to last quantifiable measurement with and without rucaparib were: caffeine, 2...
November 14, 2018: Clinical and Translational Science