Excretion mass balance and quantitative whole‐body autoradiography following a single oral (PO) administration of [14C]MSDC 0602, an mTOT‐modulating insulin sensitizer, in Sprague Dawley (SD) and Long‐Evans (LE) rats

Abstract

The objectives of this study were to determine the mass balance excretion, plasma pharmacokinetics and tissue distribution of radioactivity following PO administration of [14C]MSDC‐0602 in rats. Five groups of male SD rats and 1 group of male LE rats (28 total rats) that weighed approximately 250 g were dosed. All rats were administered a single PO bolus of [14C]MSDC‐0602 as a suspension at a dose of 10 mg/kg (50 μCi/kg). Excretion of radioactivity was rapid, with the majority eliminated within 24 h post‐dose. Biliary excretion was the primary route of elimination in bile duct‐cannulated (BDC) rats. Total recovery in urine and bile in BDC rats suggested the extent of oral absorption was at least 60%. Urinary recovery of radioactivity from intact rats (22.4%) was higher than in BDC rats (12.3%), and total radioactivity recovered in feces (31.7%) and bile (48.1%) was higher in the BDC rats (79.8%) than in the feces of intact rats (67.0%), suggesting enterohepatic recirculation of radioactivity. Plasma radioactivity had a Tmax of 8 h and declined with a t1/2 of 14.6 h. [14C]MSDC‐0602‐derived radioactivity was widely distributed; tissues levels were lower than blood through 192 h post‐dose in LE rats.