Disposition of ¹⁴C‐dapoxetine in rats: Complementary experiments with whole‐body autoradiographic and tissue dissection techniques

Abstract

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.

Recent Advances in the Applications of Radioisotopes in Drug Metabolism,Toxicology and Pharmacokinetics

“…The new scintillator originally in a soluble form quickly transforms to a solid homogenous film following exposure to room air. It enables the plates to be Bernstein and co-workers have utilized tissue dissection and WBA techniques in a complimentary manner to study the disposition of dapoxetine in Fischer 344 rats [43]. [ 14 C] Dapoxetine, a potent Fig.…”