Food increased the bioavailability of BMS-690514, an orally active EGFR/HER2/VEGF receptor kinase inhibitor, in healthy subjects

Journal of Clinical Pharmacology

Volumn 52, Issue 9, 2012, Pages 1350-1356

  Vakkalagadda, Blisse ^a   Park, Jong Soon ^a   Ahlers, Christoph M ^a   Dorizio, Stephanie ^a   Has, Teresa ^a   Roongta, Vikram ^a   Heller, Kevin N ^a   Derbin, George M ^a   Zhang, Steven ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

absorption; BMS 690514; efflux transporters; food effect; pharmacokinetics; safety

Indexed keywords

BMS 690514; CARBOHYDRATE; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ACNE; ACNE PUSTULAR; ADULT; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIARRHEA; DIET RESTRICTION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG ERUPTION; DRUG FATALITY; DRUG SAFETY; DRUG TOLERABILITY; DRY SKIN; FEMALE; FIRST PASS EFFECT; FOOD DRUG INTERACTION; GASTROINTESTINAL SYMPTOM; HUMAN; MALE; NORMAL HUMAN; OPEN STUDY; PLASMA CONCENTRATION-TIME CURVE; QUANTITATIVE ANALYSIS; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; UNSPECIFIED SIDE EFFECT;

ADULT; BIOLOGICAL AVAILABILITY; CROSS-OVER STUDIES; FEMALE; FOOD; FOOD-DRUG INTERACTIONS; HUMANS; MALE; MIDDLE AGED; PIPERIDINES; PYRROLES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; TRIAZINES; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84866040874     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270011417826     Document Type: Article

References (27)

1. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005 ; 5: 341-354
2. Arteaga CL, O'Neill A, Moulder SL, et al. A phase I-II study of combined blockade of the ErbB receptor network with trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic breast cancer. Clin Cancer Res. 2008 ; 14: 6277-6283
3. Baselga J. Combined anti-EGF receptor and anti-HER2 receptor therapy in breast cancer: a promising strategy ready for clinical testing. Ann Oncol. 2002 ; 13: 8-9
4. Wheatley-Price P, Shepherd FA. Epidermal growth factor receptor inhibitors in the treatment of lung cancer: reality and hopes. Curr Opin Oncol. 2008 ; 20: 162-175
5. Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008 ; 358: 2039-2049
6. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 ; 10: 25-34
7. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008 ; 8: 579-591
8. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 ; 356: 125-134
9. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 ; 359: 378-390
10. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006 ; 24: 16-24
11. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 ; 355: 2542-2550
12. Welch S, Spithoff K, Rumble RB, Maroun J. Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review. Ann Oncol. 2010 ; 21: 1152-1162
13. Loriot Y, Mordant P, Dorvault N, et al. BMS-690514, a VEGFR and EGFR tyrosine kinase inhibitor, shows anti-tumoural activity on non-small-cell lung cancer xenografts and induces sequence-dependent synergistic effect with radiation. Br J Cancer. 2010 ; 103: 347-353
14. Fleisher D, Li C, Zhou Y, Pao LH, Karim A. Drug, meal and formulation interactions influencing drug absorption after oral administration: clinical implications. Clin Pharmacokinet. 1999 ; 36: 233-254
15. Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005 ; 22: 11-23
16. Marathe P, Tang Y, Sleczka B, et al. Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 ; 98: 3579-3593
17. Christopher LJ, Hong H, Vakkalagadda B, et al. Metabolism and disposition of [14C]BMS-690514 ((3R,4R)-4-amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1- f][1,2,4]triazin-5-yl)methyl)-3-piperidinol), an ErbB/VEGFR inhibitor, after oral administration to humans. Drug Metab Dispos. 2010 ; 38: 2049-2059
18. Custodio JM, Wu CY, Benet LZ. Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption. Adv Drug Deliv Rev. 2008 ; 60: 717-733
19. South San Francisco. California: Genentech Inc ; 2010:
20. Singh BN. Effect of food on clinical pharmacokinetics. Clin Pharmacokinet. 1999 ; 37: 213-255
21. Kane RC, Farrell AT, Saber H, et al. Sorafenib for the treatment of advanced renal cell carcinoma. Clin Cancer Res. 2006 ; 12: 7271-7278
22. Wayne. New Jersey: Bayer HealthCare Pharmaceuticals ; 2009:
23. Research Triangle Park. North Carolina: GlaxoSmithKline ; 2010:
24. New York: Pfizer Inc ; 2010:
25. California: OSI Pharmaceuticals Inc and Genentech Inc ; 2010:
26. Delaware: AstraZeneca ; 2005:
27. North Carolina: GlaxoSmithKline ; 2010: