Fugang Wang1, Juan Cao1, Xueqin Hou1, Zhiyong Li2, Xiaolan Qu1. 1. a School of Pharmacy , Taishan Medical University , Taian , People's Republic of China. 2. b Department of Pharmacology , China Minority Traditional Medical Center of Min Zu University of China , Beijing , People's Republic of China.
Abstract
OBJECTIVE: In order to characterize the pharmacokinetics, tissue distribution, bioavailability, and excretion of nuciferine, a reliable gradient LC/MS/MS-based method was developed and validated. METHODS: Sprague-Dawley rats were intravenously injected with a bolus of nuciferine (0.2 mg/kg) and orally given a single dose of nuciferine (10.0 mg/kg). Blood samples were withdrawn via the ocular vein at specific times. Organs, including the liver, kidney, brain, lung, heart, and spleen, were collected at specific times after oral administration of 10.0 mg/kg nuciferine. The plasma and tissue samples were assayed by LC/MS/MS. RESULTS: The results indicated that nuciferine had rapid distribution and poor absorption into systemic circulation. The value of absolute bioavailability was only 1.9 ± 0.8% after administration of 10.0 mg/kg nuciferine by oral and administration of 0.2 mg/kg nuciferine intravenously (IV) to rats. The AUC0→4 h values in tissues were in the order of kidney > lung > spleen > liver > brain > heart. The majority of excretion of nuciferine (50.7%) was excreted through kidneys with parent drug after oral administration without liver metabolism. CONCLUSION: This study may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines.
OBJECTIVE: In order to characterize the pharmacokinetics, tissue distribution, bioavailability, and excretion of nuciferine, a reliable gradient LC/MS/MS-based method was developed and validated. METHODS:Sprague-Dawley rats were intravenously injected with a bolus of nuciferine (0.2 mg/kg) and orally given a single dose of nuciferine (10.0 mg/kg). Blood samples were withdrawn via the ocular vein at specific times. Organs, including the liver, kidney, brain, lung, heart, and spleen, were collected at specific times after oral administration of 10.0 mg/kg nuciferine. The plasma and tissue samples were assayed by LC/MS/MS. RESULTS: The results indicated that nuciferine had rapid distribution and poor absorption into systemic circulation. The value of absolute bioavailability was only 1.9 ± 0.8% after administration of 10.0 mg/kg nuciferine by oral and administration of 0.2 mg/kg nuciferine intravenously (IV) to rats. The AUC0→4 h values in tissues were in the order of kidney > lung > spleen > liver > brain > heart. The majority of excretion of nuciferine (50.7%) was excreted through kidneys with parent drug after oral administration without liver metabolism. CONCLUSION: This study may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines.
Entities:
Keywords:
Nuciferine; bioavailability; excretion; pharmacokinetic; tissue distribution