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 10mg/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 10mg/kg. The results suggested that the pharmacokinetic properties of SNX-2112 fitted well into a two-compartment open model with t_1/2β values of 9.96±4.32, 10.43±4.06, 10.41±4.38h 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 10mg/kg, respectively. Approximately 0.13±0.09% and 3.62±0.77% of SNX-2112 were excreted via the urine and feces within 72h, respectively; 2.59±0.67% was excreted into the bile up to 24h after a single i.v. injection of 10mg/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.