Pharmacokinetics and tissue distribution of psammaplin A, a novel anticancer agent, in mice
| Autor: | Won Sik Seo, Tae Hwan Kim, Eun Sook Ma, Beom Soo Shin, Sang Hoon Joo, Sun Dong Yoo, Il Han Kim, Soyoung Shin, Hak Jae Kim, Eun-Seok Park |
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| Rok vydání: | 2012 |
| Předmět: |
Male
DNA Methyltransferase Inhibitor Antineoplastic Agents Pharmacology urologic and male genital diseases Histone Deacetylases Mice Drug Stability Pharmacokinetics In vivo Drug Discovery medicine Animals Tissue Distribution Disulfides Lung cancer DNA Modification Methylases Mice Inbred ICR Kidney Lung Chemistry Organic Chemistry Half-life medicine.disease In vitro Histone Deacetylase Inhibitors medicine.anatomical_structure Injections Intravenous Tyrosine Molecular Medicine Half-Life |
| Zdroj: | Archives of Pharmacal Research. 35:1849-1854 |
| ISSN: | 1976-3786 0253-6269 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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