PMID- 31927013 OWN - NLM STAT- MEDLINE DCOM- 20201208 LR - 20201214 IS - 1873-6971 (Electronic) IS - 0367-326X (Linking) VI - 142 DP - 2020 Apr TI - Pharmacokinetics, tissue distribution and excretion study of Oroxylin A, Oroxylin A 7-O-glucuronide and Oroxylin A sodium sulfonate in rats after administration of Oroxylin A. PG - 104480 LID - S0367-326X(19)32374-3 [pii] LID - 10.1016/j.fitote.2020.104480 [doi] AB - Oroxylin A (OA), as a natural flavonoid extracted from the root of Scutellaria baicalensis Georgi, is a candidate drug with multiple pharmacological activities. However, pharmacokinetic studies of OA have rarely been reported up to now. The present study aim to conduct a systemic evaluation on the pharmacokinetics, tissue distribution and excretion of OA in rats, with quantification of both OA and its two metabolites, Oroxylin A 7-O-glucuronide (OG) and Oroxylin A sodium sulfonate (OS) by the sensitive and rapid UPLC-MS/MS methods. The results show that OA was rapidly eliminated in vivo after a single-dose (2 mg/kg) i.v. administration of OA. The relative bioavailability of OA in all three i.g. administration groups (40, 120, and 360 mg/kg) were <2%. The AUC(0-t) values of OA, OG, and OS in rats show an apparent dose-proportionality. OA, OG, and OS all underwent a rapid and widespread tissue distribution after i.g. administration (120 mg/kg) of OA. Except for stomach and intestine, the major distribution tissues of OA and its two metabolites in rats were liver, kidney, respectively. And OA was more widely distributed in tissue than its metabolites. After i.g. administration (120 mg/kg) of OA, it was mainly excreted from the feces, and OG mainly excreted from bile and urine, while OS almost free of excretion. This work present a comprehensive pharmacokinetics information for further investigation of OA and its two metabolites. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Ren, Guanghui AU - Ren G AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Chen, Huili AU - Chen H AD - School of Engineering & Applied Science, Yale University, New Haven, CT 06520, United States. FAU - Zhang, Mei AU - Zhang M AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Yang, Nan AU - Yang N AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Yang, Hui AU - Yang H AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Xu, Chuanru AU - Xu C AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Li, Jiaming AU - Li J AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Ning, Chen AU - Ning C AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Song, Zhongjin AU - Song Z AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Zhou, Shiyu AU - Zhou S AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Bian, Yueying AU - Bian Y AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Lu, Yang AU - Lu Y AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Li, Ning AU - Li N AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Zhang, Yongjie AU - Zhang Y AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. FAU - Chen, Xijing AU - Chen X AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. Electronic address: chenxj-lab@hotmail.com. FAU - Zhao, Di AU - Zhao D AD - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China. Electronic address: zh_d99@cpu.edu.cn. LA - eng PT - Journal Article DEP - 20200109 PL - Netherlands TA - Fitoterapia JT - Fitoterapia JID - 16930290R RN - 0 (Flavones) RN - 0 (Flavonoids) RN - 0 (Glucuronides) RN - 0 (Tetracyclines) RN - 0 (oroxylin A-7-O-glucuronide) RN - 2176O1M292 (penimocycline) RN - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one) RN - 7C782967RD (Ampicillin) SB - IM MH - Administration, Oral MH - Ampicillin/analogs & derivatives MH - Animals MH - Area Under Curve MH - Bile/chemistry MH - Chromatography, Liquid MH - Feces/chemistry MH - Female MH - Flavones/chemistry/*metabolism/urine MH - Flavonoids/chemistry/*metabolism/*pharmacokinetics/urine MH - Glucuronides/chemistry/*metabolism/urine MH - Half-Life MH - Male MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Tandem Mass Spectrometry MH - Tetracyclines MH - Tissue Distribution OTO - NOTNLM OT - Excretion OT - Oroxylin A OT - Oroxylin A 7-O-glucuronide OT - Oroxylin A sodium sulfonate OT - Pharmacokinetics OT - Scutellaria baicalensis Georgi OT - Tissue distribution COIS- Declaration of Competing Interest The authors declare no competing financial interest. EDAT- 2020/01/14 06:00 MHDA- 2020/12/15 06:00 CRDT- 2020/01/14 06:00 PHST- 2019/12/03 00:00 [received] PHST- 2020/01/07 00:00 [revised] PHST- 2020/01/08 00:00 [accepted] PHST- 2020/01/14 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/01/14 06:00 [entrez] AID - S0367-326X(19)32374-3 [pii] AID - 10.1016/j.fitote.2020.104480 [doi] PST - ppublish SO - Fitoterapia. 2020 Apr;142:104480. doi: 10.1016/j.fitote.2020.104480. Epub 2020 Jan 9.