Pharmacokinetic disposition of apicidin possessing histone deacetylase inhibiting activities

The objective of this study was to characterize the absorption and pharmacokinetic disposition of novel cyclic tetrapeptide, apicidin, in rats. Apicidin was administered to SD rats by i.v. bolus injection (1,2 or 4 mg/kg) and oral gavages (10 mg/kg). Serum levels of apicidin were monitored by LC/MS over 8 hours following each administration. Upon i.v. injection, serum levels of apicidin were best fit by a multi-exponential equation. The t$\frac{1}{2}$. Cl$\sub$s/ and V$\sub$ss/ ranged from 0.9-1.1 hr, 52.8-56.5 ml/min/kg, and 2.6-2.7 L/kg, respectively. (omitted)