title: The Disposition of Oxymatrine in the Vascularly Perfused Rat Intestine-Liver Preparation and Its Metabolism in Rat Liver Microsomes.
abstract: The study was aimed to investigate the absorption and metabolism of oxymatrine (OMT) which contributed to its poor bioavailability. Determinations of OMT absorption and metabolism in rats were evaluated using techniques of the in situ perfused rat intestine-liver preparation and recirculated intestine preparation. Furthermore, chemical inhibition experiments in rat liver microsomes were used to determine the principal cytochrome P450 (CYP) isoforms involved in OMT metabolism. In the intestine-liver preparation, the steady state liver extraction ratio (0.753 ± 0.054) of OMT was 33 times higher than that for the intestine (0.023 ± 0.002). The portal vein mainly consisted of OMT, and was devoid of the metabolite matrine, whereas both OMT and matrine were detected in hepatic vein. With the intestine preparation, the extent of OMT absorption at the end of 120 min of perfusion was 4.79 ± 0.352%. The first-order rate constant for OMT absorption was 0.05 ± 0.003 min(-1). The inhibitor of CYP3A2 had strong inhibitory effect on OMT metabolism in a concentration-dependent manner, and value was reduced to 29.73% of control. The 2 perfusion techniques indicated that poor bioavailability of OMT in rats is due mostly to poor absorption and higher hepatic elimination and CYP3A2 appears to contribute to OMT metabolism in rat liver.
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Li Hua
authors: LH
authors: Huang
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Yun Ming
authors: YM
authors: Zhong
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Xiao Hong
authors: XH
authors: Xiong
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Mei Feng
authors: MF
authors: Cen
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Xuan Ge
authors: XG
authors: Cheng
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Gui Xiang
authors: GX
authors: Wang
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Ji Sheng
authors: JS
authors: Chen
authors: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: wsj7272@126.com.
authors: Su Jun
authors: SJ
authors: Wang
mesh_terms: D000470:Alkaloids / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006503:Hepatic Veins / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion / Q000379:methods*; D011807:Quinolizines / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000093842:Matrines
chemical_list: D000470:Alkaloids; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines
keywords: absorption; in situ vascularly perfused rat intestine-liver preparation; matrine (PubChem CID: 285698); metabolism; oxymatrine (PubChem CID: 114850); recirculated intestine preparation