Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats
10-Dehydroxyl-12-demethoxy-conophylline is a natural anticancer candidate. The motivation of this study was to explore the pharmacokinetic profiles, tissue distribution, and plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline in Sprague Dawley rats. A rapid, sensitive, and specific ult...
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MDPI AG
2019-01-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/24/2/283 |
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| author | Chengjun Jiang Jie Li Xianghai Cai Nini Li Yan Guo Dianlei Wang |
| author_facet | Chengjun Jiang Jie Li Xianghai Cai Nini Li Yan Guo Dianlei Wang |
| author_sort | Chengjun Jiang |
| collection | DOAJ |
| description | 10-Dehydroxyl-12-demethoxy-conophylline is a natural anticancer candidate. The motivation of this study was to explore the pharmacokinetic profiles, tissue distribution, and plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline in Sprague Dawley rats. A rapid, sensitive, and specific ultra-performance liquid chromatography (UPLC) system with a fluorescence (FLR) detection method was developed for the determination of 10-dehydroxyl-12-demethoxy-conophylline in different rat biological samples. After intravenous (i.v.) dosing of 10-dehydroxyl-12-demethoxy-conophylline at different levels (4, 8, and 12 mg/kg), the half-life t1/2α of intravenous administration was about 7 min and the t1/2β was about 68 min. The AUC0→∞ increased in a dose-proportional manner from 68.478 μg/L·min for 4 mg/kg to 305.616 mg/L·min for 12 mg/kg. After intragastrical (i.g.) dosing of 20 mg/kg, plasma levels of 10-dehydroxyl-12-demethoxy-conophylline peaked at about 90 min. 10-dehydroxyl-12-demethoxy-conophyllinea absolute oral bioavailability was only 15.79%. The pharmacokinetics process of the drug was fit to a two-room model. Following a single i.v. dose (8 mg/kg), 10-dehydroxyl-12-demethoxy-conophylline was detected in all examined tissues with the highest in kidney, liver, and lung. Equilibrium dialysis was used to evaluate plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline at three concentrations (1.00, 2.50, and 5.00 µg/mL). Results indicated a very high protein binding degree (over 80%), reducing substantially the free fraction of the compound. |
| first_indexed | 2024-12-10T22:03:14Z |
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| language | English |
| last_indexed | 2024-12-10T22:03:14Z |
| publishDate | 2019-01-01 |
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| series | Molecules |
| spelling | doaj.art-5deaaa2c031447428e57ebbbbd81c8c32022-12-22T01:31:51ZengMDPI AGMolecules1420-30492019-01-0124228310.3390/molecules24020283molecules24020283Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in RatsChengjun Jiang0Jie Li1Xianghai Cai2Nini Li3Yan Guo4Dianlei Wang5School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, ChinaSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, ChinaSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, ChinaSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, ChinaSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China10-Dehydroxyl-12-demethoxy-conophylline is a natural anticancer candidate. The motivation of this study was to explore the pharmacokinetic profiles, tissue distribution, and plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline in Sprague Dawley rats. A rapid, sensitive, and specific ultra-performance liquid chromatography (UPLC) system with a fluorescence (FLR) detection method was developed for the determination of 10-dehydroxyl-12-demethoxy-conophylline in different rat biological samples. After intravenous (i.v.) dosing of 10-dehydroxyl-12-demethoxy-conophylline at different levels (4, 8, and 12 mg/kg), the half-life t1/2α of intravenous administration was about 7 min and the t1/2β was about 68 min. The AUC0→∞ increased in a dose-proportional manner from 68.478 μg/L·min for 4 mg/kg to 305.616 mg/L·min for 12 mg/kg. After intragastrical (i.g.) dosing of 20 mg/kg, plasma levels of 10-dehydroxyl-12-demethoxy-conophylline peaked at about 90 min. 10-dehydroxyl-12-demethoxy-conophyllinea absolute oral bioavailability was only 15.79%. The pharmacokinetics process of the drug was fit to a two-room model. Following a single i.v. dose (8 mg/kg), 10-dehydroxyl-12-demethoxy-conophylline was detected in all examined tissues with the highest in kidney, liver, and lung. Equilibrium dialysis was used to evaluate plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline at three concentrations (1.00, 2.50, and 5.00 µg/mL). Results indicated a very high protein binding degree (over 80%), reducing substantially the free fraction of the compound.http://www.mdpi.com/1420-3049/24/2/28310-dehydroxyl-12-demethoxy-conophyllinepharmacokineticstissue distributionprotein binding rate |
| spellingShingle | Chengjun Jiang Jie Li Xianghai Cai Nini Li Yan Guo Dianlei Wang Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats Molecules 10-dehydroxyl-12-demethoxy-conophylline pharmacokinetics tissue distribution protein binding rate |
| title | Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats |
| title_full | Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats |
| title_fullStr | Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats |
| title_full_unstemmed | Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats |
| title_short | Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats |
| title_sort | pharmacokinetics tissue distribution plasma protein binding studies of 10 dehydroxyl 12 demethoxy conophylline a novel anti tumor candidate in rats |
| topic | 10-dehydroxyl-12-demethoxy-conophylline pharmacokinetics tissue distribution protein binding rate |
| url | http://www.mdpi.com/1420-3049/24/2/283 |
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