Preclinical pharmacokinetic analysis of SNX-2112, a novel Hsp90 inhibitor, in rats

SNX-2112 is a novel Hsp90 inhibitor. The aim of this study was to investigate the pharmacokinetics, tissue distribution, plasma protein binding and excretion profiles of SNX-2112 in Sprague-Dawley rats after a single intravenous injection. The pharmacokinetic properties of SNX-2112 were examined after a single i.v. injection of 2.5, 5, and 10 mg/kg to rats, respectively. The tissue distribution and urinary, fecal, and biliary excretion patterns of SNX-2112 were investigated following a single i.v. injection of 10 mg/kg. The results suggested that the pharmacokinetic properties of SNX-2112 fitted well into a two-compartment open model with t1/2β values of 9.96 ± 4.32, 10.43 ± 4.06, 10.41 ± 4.38 h and area under the curve values of 7.62 ± 1.03, 8.10 ± 0.77, 15.80 ± 1.00 (μg/mL) h according to the single doses of 2.5, 5, and 10 mg/kg, respectively. Approximately 0.13 ± 0.09% and 3.62 ± 0.77% of SNX-2112 were excreted via the urine and feces within 72 h, respectively; 2.59 ± 0.67% was excreted into the bile up to 24 h after a single i.v. injection of 10 mg/kg. The major elimination route was therefore through excretion in the feces. The binding rate of SNX-2112 with plasma protein was found to be concentration-dependent. In conclusion, this study first provided the full pharmacokinetic characteristics and tissue distribution of SNX-2112, which would be helpful for its clinical regiment design.