Effects of rifampin and ketoconazole on the pharmacokinetics of nilotinib in healthy participants

Journal of Clinical Pharmacology

Volumn 51, Issue 1, 2011, Pages 75-83

  Tanaka, Chiaki ^a   Yin, Ophelia Q P ^a   Smith, Tom ^b   Sethuraman, Venkat ^a   Grouss, Karen ^a   Galitz, Lawrence ^c   Harrell, Robert ^d   Schran, Horst ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^c South Florida Bioavailability Clinic   (United States)

^d Arkansas Research Medical Testing LLC   (United States)

Author keywords

CYP3A4 induction; CYP3A4 inhibition; Nilotinib; pharmacokinetics

Indexed keywords

6BETA HYDROXYHYDROCORTISONE; HYDROCORTISONE; KETOCONAZOLE; NILOTINIB; RIFAMPICIN;

ADULT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DIZZINESS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFECT; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HEADACHE; HUMAN; HUMAN EXPERIMENT; HUMAN TISSUE; INCREASED APPETITE; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; SINGLE DRUG DOSE; SINUS CONGESTION; VOMITING;

ADULT; AREA UNDER CURVE; CYTOCHROME P-450 CYP3A; DRUG INTERACTIONS; ENZYME INDUCTION; ENZYME INHIBITORS; FEMALE; HUMANS; HYDROCORTISONE; KETOCONAZOLE; MALE; PYRIMIDINES; RIFAMPIN; YOUNG ADULT;

EID: 78649304183     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270010367428     Document Type: Article

References (28)

1. 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: 1765-1769.
2. Verstovsek S., Golemovic M., Kantarjian H., et al. AMN107, a novel aminopyrimidine inhibitor of p190 Bcr-Abl activation and of in vitro proliferation of Philadelphia-positive acute lymphoblastic leukemia cells. Cancer. 2005 ; 104: 1230-1236.
3. Weisberg E., Manley PW, Breitenstein W., et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005 ; 7: 129-141.
4. Golemovic M., Verstovsek S., Giles F., et al. AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity against imatinib-resistant chronic myeloid leukemia. Clin Cancer Res. 2005 ; 11: 4941-4947.
5. Deremer DL, Ustun C., Natarajan K. Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia. Clin Ther. 2008 ; 30: 1956-1975.
6. Hazarika M., Jiang X., Liu Q., et al. Tasigna for chronic and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukemia resistant to or intolerant of imatinib. Clin Cancer Res. 2008 ; 14: 5325-5331.
7. Kantarjian H., Giles F., Bhalla K., et al. Nilotinib in chronic myeloid leukemia patients in chronic phase (CML-CP) with imatinib resistance or intolerance: 24-month follow-up results of a phase 2 study. Haematologica. 2009 ; 94: 254-255.
8. Kantarjian H., Giles F., Wunderle L., et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 ; 354: 2542-2551.
9. Tanaka C., Yin OQ, Sethuraman V., et al. Clinical pharmacokinetics of the BCR-ABL tyrosine kinase inhibitor nilotinib. Clin Pharmacol Ther. 2010 ; 87: 197-203.
10. Tasigna (nilotinib) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation ; 2007.
11. Gashaw I., Kirchheiner J., Goldammer M. Cytochrome P4503A4 messenger ribonucleic acid induction by rifampin in human peripheral blood mononuclear cells: correlation with alprazolam pharmacokinetics. Clin Pharmacol Ther. 2003 ; 74: 448-457.
12. Chen J., Raymond K. Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor. Ann Clin Microbiol Antimicrob. 2006 ; 5: 3.
13. Greimer B., Eichelbaun M., Fritz P., et al. The interaction of digoxin and rifampin: role of intestinal P-glycoprotein. J Clin Invest. 1999 ; 104: 147-153.
14. Westphal K., Weinbrenner A., Zschiesche M., et al. Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction. Clin Pharmacol Ther. 2000 ; 68: 345-355.
15. Achira M., Suzuki H., Ito K., Sugiyama Y. Comparative studies to determine the selective inhibitors for P-glycoprotein and cytochrome P4503A4. AAPS PharmSci. 1999 ; 1: E18.
16. Niemi M., Beckman JT, Fromm MF, Neuvonen PJ, Kivisto KT Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharmacokinet. 2003 ; 42: 819-850.
17. Dresser GK, Spence JD, Bailey DG Pharmacokineticpharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000 ; 38: 41-57.
18. Bjornsson TD, Callaghan JT, Einolf HJ, et al. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol. 2003 ; 43: 443-469.
19. US Food and Drug Administration (FDA). Guidance for Industry: Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling. http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4079B1-04- Topic2-TabA.pdf. Accessed September 3, 2009.
20. Tran JQ, Kovacs SJ, McIntosh TS, Davis HM, Martin DE Morning spot and 24-hour urinary 6 beta-hydroxycortisol to cortisol ratios: intraindividual variability and correlation under basal conditions and conditions of CYP 3A4 induction. J Clin Pharmacol. 1999 ; 39: 487-494.
21. Yin OQ, Shi X., Tomlinson B., Chow MS Interindividual and intraindividual variability of the urinary 6beta-hydroxycortisol/ cortisol ratio in Chinese subjects: implications of its use for evaluating CYP3A activity. J Clin Pharmacol. 2004 ; 44: 1412-1417.
22. Olkkola KT, Backman JT, Neuvonen PJ Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole and itraconazole. Clin Pharmacol Ther. 1994 ; 55: 481-485.
23. Yeo KP, Lowe SL, Lim MT, Voelker JR, Burkey JL, Wise SD Pharmacokinetics of ruboxistaurin are significantly altered by rifampin-mediated CYP3A4 induction. Br J Clin Pharmacol. 2006 ; 61: 200-210.
24. Mahon FX, Hayette S., Lagarde V., et al. Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer Res. 2008 ; 68: 9809-9816.
25. Davies A., Jordanides NE, Giannoudis A., et al. Nilotinib concentration in cell lines and primary CD34+ chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters. Leukemia. 2009 ; 23: 1999-2006.
26. Westphal K., Weinbrenner A., Zschiesche M., et al. Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction. Clin Pharmacol Ther. 2000 ; 68: 345-355.
27. Varhu A., Olkkola KT, Neuvonen PJ Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole and itraconazole. Clin Pharmacol Ther. 1994 ; 56 (pt 1). 601-607.
28. Yin OQ, Gallagher N., Li A., Zhou W., Harrell R., Schran H. Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants. J Clin Pharmacol. 2010 ; 50: 188-194.