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KMID : 0043320120350101849
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Archives of Pharmacal Research
2012 Volume.35 No. 10 p.1849 ~ p.1854
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Pharmacokinetics and tissue distribution of psammaplin A, a novel anticancer agent, in mice
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Kim Hak-Jae
Kim Tae-Hwan
Seo Won-Sik
Yoo Sun-Dong
Kim Il-Han
Joo Sang-Hoon
Shin So-Young
Park Eun-Seok
Ma Eun-Sook
Shin Beom-Soo
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Abstract
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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 (t1/2, λn) of 9.9 ± 1.4 min and the systemic clearance (CLs) of 925.1 ± 570.1 mL/min. The in vitro stability of PsA was determined in different tissue homogenates. The average degradation t1/2 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 (Kp) 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.
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KEYWORD
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Psammaplin A, Pharmacokinetics, Tissue distribution, Stability
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