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Molecules 2019, 24(2), 283; https://doi.org/10.3390/molecules24020283

Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats

1,†
,
1,2,†
,
3
,
1
,
1
and
1,*
1
School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China
2
School of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China
3
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 10 December 2018 / Revised: 9 January 2019 / Accepted: 10 January 2019 / Published: 14 January 2019
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Abstract

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. View Full-Text
Keywords: 10-dehydroxyl-12-demethoxy-conophylline; pharmacokinetics; tissue distribution; protein binding rate 10-dehydroxyl-12-demethoxy-conophylline; pharmacokinetics; tissue distribution; protein binding rate
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Jiang, C.; Li, J.; Cai, X.; Li, N.; Guo, Y.; Wang, D. Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats. Molecules 2019, 24, 283.

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