Disposition and pharmacokinetics in rats of McN-5707, a potential antidepressant drug

A single 80 mg/kg oral solution dose of McN-5707-14C x HBr [trans-6-(2-chlorophenyl)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline hydrobromide (1:1)] was administered orally to 40 Wistar rats. Total 14C concentrations in plasma were high (> 4.5 μg x equiv/mL) for at least 24 hours after dosing. Unchanged McN-5707 represented < 10% of the total 14C concs in plasma at 45 min and < 1% at 24 hours after dosing. In the 8 days following dose administration, 23% of the dose was excreted in urine and 70% of the dose was excreted in feces. Analysis (HPLC and TLC) of glusulase treated urine, plasma and fecal samples revealed the presence of multiple metabolites of McN-5707. Unchanged McN-5707 was found only in fecal extracts (2-7% of dose). Single solution doses of McN-5707 x HBr were administered p.o. (20 mg/kg) and i.v. (4 mg/kg) to 39 Wistar rats. Plasma samples were analyzed for McN-5707 using a capillary GC assay. These studies indicated that McN-5707 was well absorbed and extensively metabolized in rats following oral doses