Pharmacokinetics of SD-0542, a Novel Histone Deacetylase Inhibitor, in Rats

Pharmacokinetics of SD-0542, a Novel Histone Deacetylase Inhibitor, in Rats

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This study reports the pharmacokinetics of a novel histone deacetylase inhibitor, SD-0542, in rats after i.v. and oral administration. SD-0542 was injected intravenously at doses of 10, 20, and 40 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 their values ranging from 2.0-2.5 hr, 157.2-214.1 ml/min/kg, and 11.1-17.5 L/kg, respectively, whereas, the initial serum concentration (C0) and AUC increased linearly as the dose was increased. Renal excretion of SD-0542 was minimal. Oral pharmacokinetic studies were conducted in rats at a dose of 20 mg/kg. The Tmax, Cl/F, Vz/F, and t1/2 were 2.0 hr, 92864 ml/min/kg, 16331 L/kg, and 2.0 hr, respectively. Taken together, SD-0542 showed linear pharmacokinetics over the i.v. bolus dose range studied. SD-0542 was poorly absorbed, with the absolute oral bioavailability of 0.9%.