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KMID : 0043320150380112076
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Archives of Pharmacal Research
2015 Volume.38 No. 11 p.2076 ~ p.2082
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Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats
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Kim Tae-Heon
Jeong Jong-Woo
Song Ji-Hye
Lee Kyeong-Ryoon
Ahn Sun-Joo
Ahn Sung-Hoon
Kim Sung-Sub
Koo Tae-Sung
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Abstract
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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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KEYWORD
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Enzalutamide, Pharmacokinetics, Tissue distribution, Metabolsim, Excretion
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