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Pharmacokinetics of a novel histone deacetylase inhibitor, apicidin, in rats
Author(s) -
Shin Beom Soo,
Chang Hyun Sook,
Park Eun Hye,
Yoon Chi Ho,
Kim Hye Youn,
Kim John,
Ryu Jae Kuk,
Zee Ok Pyo,
Lee Kang Choon,
Cao Dianxiu,
Yoo Sun Dong
Publication year - 2006
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.485
Subject(s) - pharmacokinetics , bioavailability , oral administration , volume of distribution , pharmacology , chemistry , absorption (acoustics) , histone deacetylase inhibitor , medicine , histone deacetylase , biochemistry , histone , physics , acoustics , gene
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 ( t 1/2 ), systemic clearance ( Cl ) and steady‐state volume of distribution ( V ss ) 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 ( C 0 ) 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 T max , Cl / F and V z / 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. Copyright © 2005 John Wiley & Sons, Ltd.