期刊
BIOMOLECULES
卷 9, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/biom9110655
关键词
7,8-dihydroxyflavone; serum albumin; cytochrome P450 enzymes; xanthine oxidase; pharmacokinetic interactions
资金
- European Union
- European Social Fund [EFOP-3.6.1, GINOP-2.3.2-15-2016-00049]
7,8-dihydroxyflavone (DHF) is a flavone aglycone which has beneficial effects in several central nervous system diseases. Most of the pharmacokinetic properties of DHF have been characterized, while only limited information is available regarding its interactions with serum albumin and biotransformation enzymes. In this study, the interactions of DHF with albumin was examined employing fluorescence spectroscopy and ultrafiltration. Furthermore, the inhibitory effects of DHF on cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and xanthine oxidase (XO) enzymes were also tested using in vitro models. Our results demonstrate that DHF forms a stable complex with albumin (K = 4.9 x 10(5) L/mol) and that it is able to displace both Site I and Site II ligands. Moreover, DHF proved to be a potent inhibitor of each enzyme tested, showing similar or slightly weaker effects than the positive controls used. Considering the above-listed observations, the coadministration of DHF with drugs may interfere with the drug therapy due to the development of pharmacokinetic interactions.
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