Distribution of perospirone to melanin in pigmented rats.

Following the administration of [Carbonyl-14C]perospirone ([CO-14C]perospirone) and [isothiazolyl-3-14C]perospirone ([TH-14C]perospirone) to male-pigmented rats at a single oral dose of 10 mg/kg, serum radioactivity reached maxima of 499 ng eq./g and 446 ng eq./g, respectively, at 1 hour, then decreased rapidly to below 2 ng eq./g at 168 hours, and radioactivity in eyeballs reached maxima of 576 ng eq./g and 3449 ng eq./g, respectively, at 24 hours, then decreasing slowly to become 120 ng eq./g and 314 ng eq./g at 26 weeks. Apparent elimination half-lives of radioactivity in eyeballs were 197 and 126 days for [CO-14C]perospirone and [TH-14C]perospirone, respectively. With radioluminograms, radioactivity was detected specifically in the uvea, reaching maxima at 168 hours for [CO-14C]perospirone and at 24 hours for [TH-14C]perospirone. In addition to unchanged compound, many metabolites were found in serum and eyeballs, but those were also detectable in SD albino rats and cynomolgus monkeys. Among radioactive components in eyeballs after administration of [CO-14C]perospirone, ratios of ID-15036 and MX11 followed by unchanged compound and MX9 are high. After administration of [TH-14C]perospirone, ID-11614 accounted for nearly half of the radioactivity. Values decreased in line with radioactivity in eyeballs over time and 26 weeks only a few polar metabolites could be detected.