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

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Cotreau MM, Hale CL, Jacobson L, Oelke CS, Strahs AL, Kochan RG, Sanga M, Slichenmyer W, Vargo DL

Clin Pharmacol Drug Dev. 2012 Jul;1(3):102-9. doi: 10.1177/2160763X12447303.

PubMed ID

27121337 [ View in PubMed

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Abstract

OBJECTIVE: To evaluate the absorption, metabolism, and excretion of tivozanib, a new investigational drug for renal cell carcinoma and solid malignancies. METHODS: Eight healthy male participants received a single 1.5-mg ( 160 muCi) dose of oral [(14) C]-tivozanib. Whole blood, serum, urine, and feces were evaluated up to 28 days postdose for pharmacokinetics, radioanalysis, and metabolites. Adverse events were recorded throughout the study. RESULTS: [(14) C]-tivozanib concentration peaked at 10.9 +/- 5.84 hours. The mean serum half-life for [(14) C]-tivozanib was 89.3 +/- 23.5 hours. The maximum concentration and area under the curve for [(14) C]-tivozanib were 12.1 +/- 5.67 ng/mL and 1084 +/- 417.0 ng.h/mL, respectively. Mean recovery of total radioactivity was 91.0% +/- 11.0%; 79.3% +/- 8.82% of the radioactivity was recovered in feces both as unchanged tivozanib and metabolites. In the urine, 11.8% +/- 4.59% was recovered only as metabolites. No unchanged tivozanib was found in the urine. CONCLUSION: Tivozanib had a long half-life with no major circulating metabolite, was well tolerated as a single dose, and was primarily eliminated via feces with no unchanged tivozanib found in urine. These pharmacokinetic data of [(14) C]-tivozanib are consistent with previous studies of unlabeled tivozanib.

DrugBank Data that Cites this Article

Drugs: Tivozanib