Abstract
We characterized the pharmacokinetics of enzalutamide, a novel anti-prostate cancer drug, in rats after intravenous and oral administration in the dose range 0.5–5 mg/kg. Tissue distribution, liver microsomal stability, and plasma protein binding were also examined. After intravenous injection, systemic clearance, volumes of distribution at steady state (Vss), and half-life (T½) remained unaltered as a function of dose, with values in the ranges of 80.4–86.3 mL/h/kg, 1020–1250 mL/kg, and 9.13–10.6 h, respectively. Following oral administration, absolute oral bioavailability was 89.7 % and not dose-dependent. The recoveries of enzalutamide in urine and feces were 0.0620 and 2.04 %, respectively. Enzalutamide was distributed primarily in 10 tissues (brain, liver, kidneys, testis, heart, spleen, lungs, gut, muscle, and adipose) and tissue-to-plasma ratios of enzalutamide ranged from 0.406 (brain) to 10.2 (adipose tissue). Further, enzalutamide was stable in rat liver microsomes, and its plasma protein binding was 94.7 %. In conclusion, enzalutamide showed dose-independent pharmacokinetics at intravenous and oral doses of 0.5–5 mg/kg. Enzalutamide distributed primarily to 10 tissues and appeared to be eliminated primarily by metabolism.
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This work was supported by the research fund of Chungnam National University.
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Tae-Heon Kim and Jong-Woo Jeong have been contributed equally to this work.
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Kim, TH., Jeong, JW., Song, JH. et al. Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats. Arch. Pharm. Res. 38, 2076–2082 (2015). https://doi.org/10.1007/s12272-015-0592-9
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DOI: https://doi.org/10.1007/s12272-015-0592-9