| English |
|---|
| Title | Saturation Pharmacokinetics of Sedative Agent, JM-1232(-)((-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta[f]isoindole-1(2H)-one) at High-Dose in Rats |
|---|
| Subtitle | |
|---|
| Authors | Ryuji Kato*, Rika Nakano*, Haruna Miki*, Seiko Suzuki*, Eriko Setta*, Yoko Urashima*, Yuka Kohda**, Tetsuya Hayashi***, Hitoshi Matsumura**, Yoshio Ijiri*, Kazuhiko Tanaka* |
|---|
| Authors(kana) | |
|---|
| Organization | *Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sciences, **Laboratories of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, ***Department of Internal Medicine III, Osaka Medical College |
|---|
| Journal | Circulation Control |
|---|
| Volume | 31 |
|---|
| Number | 3 |
|---|
| Page | 196-201 |
|---|
| Year/Month | 2010/12 |
|---|
| Article | Original article |
|---|
| Publisher | Japan Society of Circulation Control in Medicine |
|---|
| Abstract | 「Abstract」JM-1232(-)((-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta[f]isoindole-1(2H)-one) is a novel isoindoline chemical compound that affects benzodiazepine receptors, and is considered for application as a new sedative or intravenous anesthetic agent. To investigate the safety of JM-1232(-), preclinical studies investigating the pharmacokinetics of normal- and high-dose JM-1232(-) are needed. In this study, we used high performance liquid chromatography (HPLC) to measure the concentration of JM-1232(-) in plasma, and investigated the pharmacokinetics of low- to high-dose JM-1232(-) in rats. The effects of bolus administration of JM-1232(-)(1, 10, 25, 50, and 75 mg/kg) on the pharmacokinetic parameters were assessed in rats. We extrapolated JM-1232(-) to be a one-compartment model within 60 minutes after bolus administration. In the 50 mg/kg group, a significant increase in the elimination rate constant was observed, which is considered to be the saturation of metabolism and/or excretion. The rats were dead in the 75 mg/kg group. Thus, JM-1232(-) administered to rats at doses above 50 mg/kg is likely toxic. |
|---|
| Practice | Basic medicine |
|---|
| Keywords | JM-1232(-), sedative agent, assay, HPLC, saturation |
|---|