Pharmacokinetics and tissue distribution of psammaplin A, a novel anticancer agent, in mice

• Published in: Archives of pharmacal research Vol. 35; no. 10; pp. 1849 - 1854
• Main Authors: Kim, Hak Jae, Kim, Tae Hwan, Seo, Won Sik, Yoo, Sun Dong, Kim, Il Han, Joo, Sang Hoon, Shin, Soyoung, Park, Eun-Seok, Ma, Eun Sook, Shin, Beom Soo
• Format: Journal Article
• Language: English
• Published: Heidelberg Pharmaceutical Society of Korea 01.10.2012; 대한약학회
• Subjects: Animals; antineoplastic agents; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; blood serum; Disulfides - blood; Disulfides - pharmacokinetics; Disulfides - pharmacology; DNA Modification Methylases - antagonists & inhibitors; Drug Stability; Half-Life; histone deacetylase; Histone Deacetylase Inhibitors - pharmacokinetics; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases - metabolism; Injections, Intravenous; intravenous injection; kidneys; liver; lung neoplasms; Male; medicinal plants; Medicine; Mice; Mice, Inbred ICR; partition coefficients; pharmacokinetics; Pharmacology/Toxicology; Pharmacy; Research Article; Tissue Distribution; Tyrosine - analogs & derivatives; Tyrosine - blood; Tyrosine - pharmacokinetics; Tyrosine - pharmacology; 약학; Psammaplin A; Stability; Tissue distribution; Pharmacokinetics
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-012-1019-5

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.