Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings
Although arctigenin (AG) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via va...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00376/full |
| _version_ | 1818110375237779456 |
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| author | Jie Li Jie Li Jie Li Xin Li Xin Li Xin Li Yu-Shan Ren Yu-Shan Ren Yuan-Yuan Lv Yuan-Yuan Lv Yuan-Yuan Lv Jun-Sheng Zhang Jun-Sheng Zhang Jun-Sheng Zhang Xiao-Li Xu Xiao-Li Xu Xiao-Li Xu Xian-Zhen Wang Xian-Zhen Wang Xian-Zhen Wang Jing-Chun Yao Jing-Chun Yao Jing-Chun Yao Gui-Min Zhang Gui-Min Zhang Zhong Liu Zhong Liu |
| author_facet | Jie Li Jie Li Jie Li Xin Li Xin Li Xin Li Yu-Shan Ren Yu-Shan Ren Yuan-Yuan Lv Yuan-Yuan Lv Yuan-Yuan Lv Jun-Sheng Zhang Jun-Sheng Zhang Jun-Sheng Zhang Xiao-Li Xu Xiao-Li Xu Xiao-Li Xu Xian-Zhen Wang Xian-Zhen Wang Xian-Zhen Wang Jing-Chun Yao Jing-Chun Yao Jing-Chun Yao Gui-Min Zhang Gui-Min Zhang Zhong Liu Zhong Liu |
| author_sort | Jie Li |
| collection | DOAJ |
| description | Although arctigenin (AG) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i.v), hypodermic injection (i.h), and sublingual (s.l) administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate < 1 h), a high absorption degree (absolute bioavailability > 100%), and a strong elimination ability (t1/2 < 2 h). The tissue distributions of AG at different time points after i.h showed that the distribution of AG in rat tissues is rapid (2.5 h to reach the peak) and wide (detectable in almost all tissues and organs). The AG concentration in the intestine was the highest, followed by that in the heart, liver, pancreas, and kidney. In vitro, AG were incubated with human, monkey, beagle dog and rat liver microsomes. The concentrations of AG were detected by UPLC-MS/MS at different time points (from 0 min to 90 min). The percentages of AG remaining in four species’ liver microsomes were human (62 ± 6.36%) > beagle dog (25.9 ± 3.24%) > rat (15.7 ± 9%) > monkey (3.69 ± 0.12%). This systematic investigation of pharmacokinetic profiles of arctigenin (AG) in vivo and in vitro is worthy of further exploration. |
| first_indexed | 2024-12-11T02:46:09Z |
| format | Article |
| id | doaj.art-593e5ae7d4974770a84a0bd42dda2e53 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T02:46:09Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-593e5ae7d4974770a84a0bd42dda2e532022-12-22T01:23:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-06-01810.3389/fphar.2017.00376271400Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo FindingsJie Li0Jie Li1Jie Li2Xin Li3Xin Li4Xin Li5Yu-Shan Ren6Yu-Shan Ren7Yuan-Yuan Lv8Yuan-Yuan Lv9Yuan-Yuan Lv10Jun-Sheng Zhang11Jun-Sheng Zhang12Jun-Sheng Zhang13Xiao-Li Xu14Xiao-Li Xu15Xiao-Li Xu16Xian-Zhen Wang17Xian-Zhen Wang18Xian-Zhen Wang19Jing-Chun Yao20Jing-Chun Yao21Jing-Chun Yao22Gui-Min Zhang23Gui-Min Zhang24Zhong Liu25Zhong Liu26Shandong New Time Pharmaceutical Co., LtdLinyi, ChinaCenter for New Drug Safety Evaluation of Lunan Pharmaceutical, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaCenter for New Drug Safety Evaluation of Lunan Pharmaceutical, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaCenter for New Drug Safety Evaluation of Lunan Pharmaceutical, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaCenter for New Drug Safety Evaluation of Lunan Pharmaceutical, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaCenter for New Drug Safety Evaluation of Lunan Pharmaceutical, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaCenter for New Drug Safety Evaluation of Lunan Pharmaceutical, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaCenter for New Drug Safety Evaluation of Lunan Pharmaceutical, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaShandong New Time Pharmaceutical Co., LtdLinyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., LtdLinyi, ChinaAlthough arctigenin (AG) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i.v), hypodermic injection (i.h), and sublingual (s.l) administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate < 1 h), a high absorption degree (absolute bioavailability > 100%), and a strong elimination ability (t1/2 < 2 h). The tissue distributions of AG at different time points after i.h showed that the distribution of AG in rat tissues is rapid (2.5 h to reach the peak) and wide (detectable in almost all tissues and organs). The AG concentration in the intestine was the highest, followed by that in the heart, liver, pancreas, and kidney. In vitro, AG were incubated with human, monkey, beagle dog and rat liver microsomes. The concentrations of AG were detected by UPLC-MS/MS at different time points (from 0 min to 90 min). The percentages of AG remaining in four species’ liver microsomes were human (62 ± 6.36%) > beagle dog (25.9 ± 3.24%) > rat (15.7 ± 9%) > monkey (3.69 ± 0.12%). This systematic investigation of pharmacokinetic profiles of arctigenin (AG) in vivo and in vitro is worthy of further exploration.http://journal.frontiersin.org/article/10.3389/fphar.2017.00376/fullarctigeninpharmacokineticsUPLC/MS/MSbioavailabilitymicrosomes |
| spellingShingle | Jie Li Jie Li Jie Li Xin Li Xin Li Xin Li Yu-Shan Ren Yu-Shan Ren Yuan-Yuan Lv Yuan-Yuan Lv Yuan-Yuan Lv Jun-Sheng Zhang Jun-Sheng Zhang Jun-Sheng Zhang Xiao-Li Xu Xiao-Li Xu Xiao-Li Xu Xian-Zhen Wang Xian-Zhen Wang Xian-Zhen Wang Jing-Chun Yao Jing-Chun Yao Jing-Chun Yao Gui-Min Zhang Gui-Min Zhang Zhong Liu Zhong Liu Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings Frontiers in Pharmacology arctigenin pharmacokinetics UPLC/MS/MS bioavailability microsomes |
| title | Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings |
| title_full | Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings |
| title_fullStr | Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings |
| title_full_unstemmed | Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings |
| title_short | Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings |
| title_sort | elucidation of arctigenin pharmacokinetics and tissue distribution after intravenous oral hypodermic and sublingual administration in rats and beagle dogs integration of in vitro and in vivo findings |
| topic | arctigenin pharmacokinetics UPLC/MS/MS bioavailability microsomes |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00376/full |
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