title: Pharmacokinetics and tissue distribution of psammaplin A, a novel anticancer agent, in mice.
abstract: This study reports the pharmacokinetics and tissue distribution of a novel histone deacetylase and DNA methyltransferase inhibitor, psammaplin A (PsA), in mice. PsA concentrations were determined by a validated LC-MS/MS assay method (LLOQ 2 ng/mL). Following intravenous injection at a dose of 10 mg/kg in mice, PsA was rapidly eliminated, with the average half-life (t(1/2, λn)) of 9.9 ± 1.4 min and the systemic clearance (CL(s)) of 925.1 ± 570.1 mL/min. The in vitro stability of PsA was determined in different tissue homogenates. The average degradation t(1/2) of PsA in blood, liver, kidney and lung was found relatively short (≤ 12.8 min). Concerning the in vivo tissue distribution characteristics, PsA was found to be highly distributed to lung tissues, with the lung-to-serum partition coefficients (K(p)) ranging from 49.9 to 60.2. In contrast, PsA concentrations in other tissues were either comparable with or less than serum concentrations. The high and specific lung targeting characteristics indicates that PsA has the potential to be developed as a lung cancer treatment agent.
authors.affiliation: Department of Radiation Oncology, Seoul National University Hospital, Korea.
authors.forename: Hak Jae
authors.initials: HJ
authors.lastname: Kim
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Seo
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
authors.forename: Il Han
authors.initials: IH
authors.lastname: Kim
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Joo
authors.forename: Soyoung
authors.initials: S
authors.lastname: Shin
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Ma
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D004220:Disulfides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004355:Drug Stability; D006207:Half-Life; D056572:Histone Deacetylase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014018:Tissue Distribution; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D056572:Histone Deacetylase Inhibitors; C098378:psammaplin A; D014443:Tyrosine; D015254:DNA Modification Methylases; D006655:Histone Deacetylases