Effects of Ketoconazole on the Pharmacokinetics of Ponatinib in Healthy Subjects

• Published in: Journal of clinical pharmacology Vol. 53; no. 9; pp. 974 - 981
• Main Authors: Narasimhan, Narayana I., Dorer, David J., Niland, Katie, Haluska, Frank, Sonnichsen, Daryl
• Format: Journal Article
• Language: English
• Published: England 01.09.2013
• Subjects: Adult; Area Under Curve; BCR‐ABL; Biological Availability; Cross-Over Studies; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - blood; Enzyme Inhibitors - pharmacokinetics; Fusion Proteins, bcr-abl - antagonists & inhibitors; Humans; Imidazoles - administration & dosage; Imidazoles - blood; Imidazoles - pharmacokinetics; ketoconazole; Ketoconazole - administration & dosage; Male; Middle Aged; pharmacokinetics; ponatinib; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyridazines - administration & dosage; Pyridazines - blood; Pyridazines - pharmacokinetics; tyrosine kinase inhibitor; Young Adult; pharmacokinetics; ketoconazole; ponatinib; tyrosine kinase inhibitor; BCR-ABL

Ponatinib is a BCR‐ABL tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia in patients resistant or intolerant to prior TKIs. In vitro studies suggested that metabolism of ponatinib is partially medi...