A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue d...A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative (8-acetamino-isocorydine) of isocorydine. According to the in vivo experiments data calculations by DAS 2.0 software, a two compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetaminoiso-corydine in rats. 8-Acetamino-isocorydine was absorbed well after oral administration, and the absolute bioavailability was 76.5%. The half-life of 8-acetamino-isocorydine after intravenous and oral administration was 2.2 h and 2.0 h, respectively. In Oro, 8-acetamino-isocorydine was highly distributed in the lungs, kidney and liver; however, relatively little entered the brain, suggesting that 8-acetaminoisocorydine could not easily pass through the blood brain bather. Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-isocorydine. The acquired data will provide useful infonnation for the in vivo pharmacology of 8-acetaminoisocorydine, and can he applied to new drug research. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia IMedica, Chinese Academy of 'Medical Sciences. Production and hosting by Elsevier B.V.展开更多
基金supported by the "West Light Program (No.Y30447YXL1)""Build Coalitions of the National Academy of Sciences" of the Chinese Academy of Sciences (No.Y20475YLJ1)the Science and Technology Program of Gansu (No.1304FKCA062)
文摘A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative (8-acetamino-isocorydine) of isocorydine. According to the in vivo experiments data calculations by DAS 2.0 software, a two compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetaminoiso-corydine in rats. 8-Acetamino-isocorydine was absorbed well after oral administration, and the absolute bioavailability was 76.5%. The half-life of 8-acetamino-isocorydine after intravenous and oral administration was 2.2 h and 2.0 h, respectively. In Oro, 8-acetamino-isocorydine was highly distributed in the lungs, kidney and liver; however, relatively little entered the brain, suggesting that 8-acetaminoisocorydine could not easily pass through the blood brain bather. Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-isocorydine. The acquired data will provide useful infonnation for the in vivo pharmacology of 8-acetaminoisocorydine, and can he applied to new drug research. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia IMedica, Chinese Academy of 'Medical Sciences. Production and hosting by Elsevier B.V.
