Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor.
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Xiao JJ, Nowak D, Ramlau R, Tomaszewska-Kiecana M, Wysocki PJ, Isaacson J, Beltman J, Nash E, Kaczanowski R, Arold G, Watkins S
Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor.
Clin Transl Sci. 2019 Jan;12(1):58-65. doi: 10.1111/cts.12600. Epub 2018 Dec 20.
- PubMed ID
- 30427584 [ View in PubMed]
- Abstract
This phase I study (CO-338-044; NCT02740712), conducted in patients with advanced solid tumors, evaluated the effect of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib on the pharmacokinetics (PK) 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 (P-gp) substrate; dosed separately) without rucaparib and following oral rucaparib 600 mg b.i.d. Geometric mean (GM) ratios (90% confidence interval (CI)) of area under the concentration-time curve (AUC) from time zero to last quantifiable measurement with and without rucaparib were: caffeine, 2.26 (1.93-2.65); S-warfarin, 1.49 (1.40-1.58); omeprazole, 1.55 (1.32-1.83); midazolam, 1.39 (1.14-1.68); and digoxin, 1.20 (1.12-1.29). There was limited effect on peak concentration of the substrates (GM ratios, 0.99-1.13). At steady state, rucaparib 600 mg b.i.d. moderately inhibited CYP1A2, weakly inhibited CYP2C9, CYP2C19, and CYP3A, and marginally increased digoxin exposure.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Rucaparib Cytochrome P450 1A2 Protein Humans NoSubstrateInhibitorInducerDetails Rucaparib Cytochrome P450 2C19 Protein Humans NoInhibitorDetails Rucaparib Cytochrome P450 2C9 Protein Humans NoInhibitorDetails Rucaparib Cytochrome P450 3A4 Protein Humans NoSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAbemaciclibRucaparib The metabolism of Abemaciclib can be decreased when combined with Rucaparib. AcalabrutinibRucaparib The metabolism of Acalabrutinib can be decreased when combined with Rucaparib. AcenocoumarolRucaparib The metabolism of Acenocoumarol can be decreased when combined with Rucaparib. AlectinibRucaparib The metabolism of Alectinib can be decreased when combined with Rucaparib. AminophyllineRucaparib The metabolism of Aminophylline can be decreased when combined with Rucaparib.