title: Pharmacokinetics of a novel histone deacetylase inhibitor, apicidin, in rats.
abstract: This study is the first report of the pharmacokinetics of a novel histone deacetylase inhibitor, apicidin, in rats after i.v. and oral administration. Apicidin was injected intravenously at doses of 0.5, 1.0, 2.0 and 4.0 mg/kg. The terminal elimination half-life (t1/2), systemic clearance (Cl) and steady-state volume of distribution (Vss) remained unaltered as a function of dose, with values in the range 0.8-1.1 h, 59.6-68.0 ml/min/kg and 2.4-2.7 l/kg, respectively. Whereas, the initial serum concentration (C0) and AUC increased linearly as the dose was increased. Taken together, the pharmacokinetics of apicidin were linear over the i.v. dose range studied. The extent of urinary and biliary excretion of apicidin was minimal (0.017%-0.020% and 0.049% +/- 0.016%, respectively). Oral pharmacokinetic studies were conducted in fasting and non-fasting groups of rats at a dose of 10 mg/kg. The Tmax, Cl/F and Vz/F were in the range 0.9-1.1 h, 520.3-621.2 ml/min/kg and 67.6-84.4 l/kg, respectively. No significant difference was observed in the oral absorption profiles between the two groups of rats. Apicidin was poorly absorbed, with the absolute oral bioavailability of 19.3% and 14.2% in fasting and non-fasting rats.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Kyeonggi-do, 440-746, Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Chang
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Park
authors.forename: Chi Ho
authors.initials: CH
authors.lastname: Yoon
authors.forename: Hye Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Jae Kuk
authors.initials: JK
authors.lastname: Ryu
authors.forename: Ok Pyo
authors.initials: OP
authors.lastname: Zee
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.forename: Dianxiu
authors.initials: D
authors.lastname: Cao
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005215:Fasting / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D007275:Injections, Intravenous; D016014:Linear Models; D008297:Male; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; C102351:apicidin