Effects of ketoconazole on the pharmacokinetics of ponatinib in healthy subjects

Journal of Clinical Pharmacology

Volumn 53, Issue 9, 2013, Pages 974-981

  Narasimhan, Narayana I ^a   Dorer, David J ^a   Niland, Katie ^a   Haluska, Frank ^a   Sonnichsen, Daryl ^a,b  

^a ARIAD PHARMACEUTICALS INC   (United States)

^b Sonnichsen Pharmaceutical Associates   (United States)

Author keywords

BCR ABL; Ketoconazole; Pharmacokinetics; Ponatinib; Tyrosine kinase inhibitor

Indexed keywords

AP 24567; CYTOCHROME P450 3A4; DRUG METABOLITE; KETOCONAZOLE; PONATINIB; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFECT; DRUG ELIMINATION; DRUG FATALITY; DRUG HALF LIFE; ELECTROCARDIOGRAM; ENZYME INHIBITION; EVENING DOSAGE; FEMALE; HEADACHE; HUMAN; LABORATORY TEST; MALE; MAXIMUM PLASMA CONCENTRATION; MORNING DOSAGE; NORMAL HUMAN; PHYSICAL EXAMINATION; PLASMA CLEARANCE; PLASMA CONCENTRATION-TIME CURVE; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE DRUG DOSE; SOMNOLENCE; TIME TO MAXIMUM PLASMA CONCENTRATION; VITAL SIGN;

BCR-ABL; KETOCONAZOLE; PHARMACOKINETICS; PONATINIB; TYROSINE KINASE INHIBITOR;

ADULT; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP3A; DRUG INTERACTIONS; ENZYME INHIBITORS; FUSION PROTEINS, BCR-ABL; HUMANS; IMIDAZOLES; KETOCONAZOLE; MALE; MIDDLE AGED; PROTEIN-TYROSINE KINASES; PYRIDAZINES; YOUNG ADULT;

EID: 84885085143     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1002/jcph.109     Document Type: Article

References (20)

1. O'Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007;110(7):2242-2249. (Pubitemid 47523141)
2. Cortes JE, Kantarjian HM, Brummendorf TH, et al. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 2011;118(17): 4567- 4576.
3. Tokarski JS, Newitt JA, Chang CY, et al. The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res. 2006;66(11):5790-5797. (Pubitemid 43927133)
4. Weisberg E, Manley P, Mestan J, Cowan-Jacob S, Ray A, Griffin JD. AMN107 (nilotinib): A novel and selective inhibitor of BCR-ABL. Br J Cancer. 2006;94(12):1765-1769. (Pubitemid 43882564)
5. Huang WS, Metcalf CA, Sundaramoorthi R, et al. Discovery of 3-[2-(imidazo[1, 2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4- methylpiperazin-1-y l)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J Med Chem. 2010, 53(12):4701-4719.
6. O'Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCRABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16(5):401-412.
7. Zhou T, Commodore L, Huang WS, et al. Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance. Chem Biol Drug Des. 2011; 77(1):1-11.
8. Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012; 367(22):2075-2088.
9. Cortes JE, Kim D-W. Pinilla-Ibarz J, et al. A pivotal phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) resistant or intolerant to dasatinib or nilotinib, or with the T315I BCR-ABL mutation: 12-Month follow-up of the PACE trial. Blood. 2012;120: Abstract 163.
10. Ponatinib (Iclusig) prescribing information. Cambridge, MA: ARIAD Pharmaceuticals, Inc; 2012.
11. Imatinib (Gleevec) prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2011.
12. Nilotinib (Tasigna) prescribing information. East Hanover, NJ. Novartis Pharmaceuticals Corporation; 2012.
13. Dasatinib (Sprycel) prescribing information. Princeton, NJ: Bristol- Myers Squibb; 2011.
14. Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clin Pharmacokinet. 2000;38(2):111-180. (Pubitemid 30122116)
15. US Department of Health and Human Services Food and Drug Administration.Drug interaction studies-study design, data analysis, implications for dosing, and labeling recommendations. 2012; http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM292362.pdf. Accessed December 18, 2012.
16. Chien JY, Lucksiri A, Ernest CS, Gorski SA, Wrighton SA, Hall SD. Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by ketoconazole. Drug Metab Dispos. 2006;34(7):1208- 1219. (Pubitemid 43922328)
17. Abbas R, Hug BA, Leister C, Burns J, Sonnichsen D. Effect of ketoconazole on the pharmacokinetics of oral bosutinib in healthy subjects. J Clin Pharmacol. 2011;51(12):1721-1727.
18. Dutreix C, Peng B, Mehring G, et al. Pharmacokinetic interaction between ketoconazole and imatinib mesylate (Glivec) in healthy subjects. Cancer Chemother Pharmacol. 2004;54(4):290- 294. (Pubitemid 39304422)
19. Johnson FM, Agrawal S, Burris H, et al. Phase 1 pharmacokinetic and drug-interaction study of dasatinib in patients with advanced solid tumors. Cancer. 2010;116(6):1582-1591.
20. Tanaka C, Yin OQ, Smith T, et al. Effects of rifampin and ketoconazole on the pharmacokinetics of nilotinib in healthy participants. J Clin Pharmacol. 2011;51(1):75-83.