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KMID : 0043320150380061138
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Archives of Pharmacal Research
2015 Volume.38 No. 6 p.1138 ~ p.1146
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Pharmacokinetics, tissue distribution and excretion of peimisine in rats assessed by liquid chromatography-tandem mass spectrometry
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Chen Lihua
Li Dongxun
Zhang Guosong
Zhang Wei
Zhang Lihua
Guan Yongmei
Zhu Weifeng
Liu Hongning
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Abstract
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Peimisine, the common ingredient of “zhebeimu” groups and “chuanbeimu” groups, is responsible for the expectorant and cough relieving effects. The aim of this study was to investigate the pharmacokinetics, tissue distribution and excretion of peimisine in male and female SD (Sprague-Dawley) rats by a rapid and sensitive LC-MS/MS (liquid chromatography-tandem mass spectrometry) method used carbamazepine as the internal standard after oral administration, carbamazepine was stated as an IS. The results showed that peimisine was slowly distributed, and eliminated from rat plasma and manifested linear dynamics in a dose range of 0.26?6.5 mg/kg. Tested by ANOVA, there were gender differences in the pharmacokinetic parameters of AUC0?t, AUC0?∞ among a single dose of 0.26, 1.3, 6.5 mg/kg (P < 0.05). Drug blood and tissue levels in male rats were significantly higher than the female counterparts after oral administration, while both the males and the females showed high drug levels in spleen, kidney, lung, liver and heart. On the other hand, the peimisine levels that can be reached in uterus, ovary, testis and brain is low. The excretion study showed that little administered peimisine (<0.7 %) was recovered in the male and female bile. Approximately 13.46 and 15.05 % were recovered in female urine and feces, while 43.07 and 7.49 % were recovered in male urine and feces, respectively, which indicated that the major elimination route of male rats was urine excretion. In addition, there was significant differences in total cumulative excretive ratio of peimisine in feces (P < 0.05) and no significant differences in the urine (P > 0.05) at a dose of 1.3 mg/kg.
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KEYWORD
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Peimisine, Pharmacokinetics, Tissue distribution, Excretion, Gender-related differences
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