Absorption, Metabolism, and Excretion of [14C]-Tivozanib, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Male Participants: A Phase I, Open-Label, Mass-Balance Study

Clinical Pharmacology in Drug Development

Volumn 1, Issue 3, 2012, Pages 102-109

  Cotreau, Monette M ^a   Hale, Christine L ^b   Jacobson, Lindsey ^a   Oelke, Claudine S ^b   Strahs, Andrew L ^a   Kochan, Robert G ^b   Sanga, Madhu ^b   Slichenmyer, William ^a   Vargo, Dennis L ^a  

^a AVEO ONCOLOGY   (United States)

^b Late Stage Developmental Services Covance Inc   (United States)

Author keywords

absorption; excretion; metabolism; pharmacokinetics; tivozanib

Indexed keywords

CARBON 14; TIVOZANIB;

ADULT; AREA UNDER THE CURVE; ARTICLE; DECREASED APPETITE; DIARRHEA; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG EXCRETION; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG URINE LEVEL; DYSPNEA; FATIGUE; GASTROINTESTINAL DISEASE; HEADACHE; HEART PALPITATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; MUSCULOSKELETAL CHEST PAIN; NORMAL HUMAN; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RADIOACTIVITY; SCINTILLATION; SIDE EFFECT; SINGLE DRUG DOSE; SLEEP QUALITY; TANDEM MASS SPECTROMETRY; TIME TO MAXIMUM PLASMA CONCENTRATION; UNPLEASANT DREAM; UPPER ABDOMINAL PAIN; VIVID DREAM;

EID: 84892116875     PISSN: 2160763X     EISSN: 21607648     Source Type: Journal    
DOI: 10.1177/2160763X12447303     Document Type: Article

References (23)

1. De Luca A,Normanno N.Tivozanib, a pan-VEGFR tyrosine kinase inhibitor for the potential treatment of solid tumors.IDrugs. 2010;13:636-645.
2. Fan F,Schimming A,Jaeger D,Podar K.Targeting the tumor microenvironment: focus on angiogenesis.J Oncol. 2012;2012:281261.
3. San Francisco, CA: Onyx Pharmaceuticals; 2011:.
4. New York: Pfizer; 2011:.
5. Bhargava P,Robinson MO.Development of second-generation VEGFR tyrosine kinase inhibitors: current status.Curr Oncol Rep. 2011;13:103-111.
6. Eskens FA,Verweij J.The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors: a review.Eur J Cancer. 2006;42:3127-3139.
7. Eskens FA,de Jonge MJ,Bhargava P, et al.Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases, in a 4-week-on, 2-week-off schedule in patients with advanced solid tumors.Clin Cancer Res. 2011;17:7156-7163.
8. Nosov D,Esteves B,Lipatov O, et al.Efficacy and safety of tivozanib (AV-951) in a phase 2 randomized discontinuation trial in patients with renal cell carcinoma.J Clin Oncol.:.
9. Nosov DA,Bhargava P,Esteves B, et al.Final analysis of the phase II randomized discontinuation trial of tivozanib (AV-951) versus placebo in patients with renal cell carcinoma.J Clin Oncol. 2011;29:4550.
10. Motzer RJ,Bhargava P,Esteves B, et al.A phase III, randomized, controlled study to compare tivozanib with sorafenib in patients (pts) with advanced renal cell carcinoma (RCC).J Clin Oncol. 2011;29:310.
11. Cotreau MM,Bhargava P,Esteves B, et al.Abstracts of the American Society for Clinical Pharmacology and Therapeutics 2011 Annual Meeting. March 2-5, 2011. Dallas, Texas, USA.Clin Pharmacol Ther. 2011;89:S1-S165.
12. US Department of Health and Human Services, US Food and Drug Administration. Title 21-food and drugs, chapter I, subchapter D, part 361-prescription drugs for human use generally recognized as safe and effective and not misbranded: drugs used in research. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=361&showFR=1. Accessed October 2011.
13. US Department of Health and Human Services, US Food and Drug Administration Center for Drug Evaluation and Research. Guidance for Industry: Safety Testing of Drug Metabolites. February2008. http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0065-GDL.pdf. Accessed October 2011.
14. Roffey SJ,Obach RS,Gedge JI,Smith DA.What is the objective of the mass balance study? A retrospective analysis of data in animal and human excretion studies employing radiolabeled drugs.Drug Metab Rev. 2007;39:17-43.
15. Shaw JP,Cheong J,Goldberg MR,Kitt MM.Mass balance and pharmacokinetics of [14C]telavancin following intravenous administration to healthy male volunteers.Antimicrob Agents Chemother. 2010;54:3365-3371.
16. The Disposition of Total Radioactivity in the Rat Following Single Oral and Single Intravenous Administration of [14C] KRN951. Cambridge, MA: AVEO Pharmaceuticals; 2011:.
17. National Cancer Institute. SEER stat fact sheets: kidney and renal pelvis. http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed October 2011.
18. Kabbinavar FF,Srinivas S,Hauke RJ, et al.Results from a phase I trial of tivozanib (AV-951) combined with temsirolimus therapy in patients with renal cell carcinoma. Poster presented at: American Society of Clinical Oncology; Chicago, IL;.
19. Rugo HS,Herbst RS,Liu G, et al.Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results.J Clin Oncol. 2005;23:5474-5483.
20. Moore M,Hirte HW,Siu L, et al.Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors.Ann Oncol. 2005;16:1688-1694.
21. Hurwitz HI,Dowlati A,Saini S, et al.Phase I trial of pazopanib in patients with advanced cancer.Clin Cancer Res. 2009;15:4220-4227.
22. Faivre S,Delbaldo C,Vera K, et al.Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer.J Clin Oncol. 2006;24:25-35.
23. Penner N,Klunk LJ,Prakash C.Human radiolabeled mass balance studies: objectives, utilities and limitations.Biopharm Drug Dispos. 2009;30:185-203.