Disposition of 14C-dapoxetine in rats: complementary experiments with whole-body autoradiographic and tissue dissection techniques.
Tissue distribution studies, utilizing whole-body autoradiography and organ dissection techniques, were conducted in male Fischer 344 rats following the oral administration of 14C-dapoxetine HCl, a potent serotonin reuptake inhibitor. The preliminary study using whole-body autoradiography proved invaluable in locating radioactivity in an organ not usually harvested in a tissue distribution study, namely the preputial gland. Selected organs, based on whole-body autoradiography findings, were dissected from rats and analyzed for radiocarbon content by liquid scintillation counting and for parent drug and N-dealkylated metabolites by extraction and HPLC analysis. Highest concentrations of radiocarbon were observed in the organs of absorption and elimination (ileum, cecum, stomach, duodenum, liver, colon, and kidney) but notable quantities were observed in the lung and preputial and Harderian glands. Most tissues had returned to background radioactive levels 72 h after dosing but persistent concentrations of radiocarbon were present in the preputial gland and liver one week after the single dose of 14C-dapoxetine. Analysis by HPLC demonstrated the presence of parent drug and N-desmethyl metabolite (nor-dapoxetine) in those organs examined; however, the majority of the radioactivity remained unidentified.
Bernstein
J R
JR
Department of Drug Metabolism and Disposition, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Manzione
B M
BM
Pohland
R C
RC
Franklin
R B
RB
D000818:Animals; D001345:Autoradiography; D001596:Benzylamines / Q000378:metabolism / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D004210:Dissection; D008297:Male; D009281:Naphthalenes / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D001596:Benzylamines; D002250:Carbon Radioisotopes; D009281:Naphthalenes; D017367:Selective Serotonin Reuptake Inhibitors; C080598:dapoxetine