Premium
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
Author(s) -
Cotreau Monette M.,
Hale Christine L.,
Jacobson Lindsey,
Oelke Claudine S.,
Strahs Andrew L.,
Kochan Robert G.,
Sanga Madhu,
Slichenmyer William,
Vargo Dennis L.
Publication year - 2012
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1177/2160763x12447303
Subject(s) - medicine , tyrosine kinase inhibitor , excretion , tyrosine kinase , vascular endothelial growth factor , metabolism , endocrinology , pharmacology , receptor , vegf receptors , cancer
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 μCi) 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.