title: Absorption mechanism of oxymatrine in cultured Madin-Darby canine kidney cell monolayers.
abstract: Context Oxymatrine (OMT) is beneficial to human health by exerting various biological effects. Objective To investigate the absorption mechanism of OMT and discover absorption enhancers using Madin-Darby canine kidney (MDCK) cell monolayers. Materials and methods Concentration effects on the transport of OMT were measured in the range of 1.0 × 10(-5)-1.0 × 10(-3) M in 2 h. Then, the effect of time, direction, temperature and pH on the transport of OMT at 10(-4) M was studied. Moreover, Papp of OMT was determined in the absence/presence of cyclosporine and surfactants at 100 μM to further confirm the relative transport mechanism. Results The Papp AP→BL ranged from (3.040 ± 0.23) × 10(-6) to (3.697 ± 0.19) × 10(-6 )cm/s as the concentration varied from 10(-5) to 10(-3) M. OMT showed similar Papp at 4 and 37 °C (p > 0.05). Increasing the apical pH 7.4 and 8.0 resulted in Papp versus pH 5.0 (p < 0.01). Furthermore, in the presence of cyclosporine and surfactants including sodium citrate, sodium dodecyl sulphate (SDS) and deoxysodium cholate, Papp was (0.318 ± 0.033) × 10(-5), (0.464 ± 0.048) × 10(-5), (0.897 ± 0.115) × 10(-5) and (1.341 ± 0.122) × 10(-5 )cm/s, respectively. In the presence of surfactants, Papp significantly increased up to 1.5-4.3-fold (p < 0.05). Discussion and conclusion OMT transport across MDCK cell monolayers was by passive diffusion. Sodium citrate, SDS and deoxysodium cholate serve as excellent absorption enhancers which are useful for the related research improving the oral bioavailability of OMT.
authors.affiliation: a School of Pharmacy , Guangdong Pharmaceutical University , Guangzhou , P.R. China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Xiong
authors.affiliation: a School of Pharmacy , Guangdong Pharmaceutical University , Guangzhou , P.R. China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Huang
authors.affiliation: a School of Pharmacy , Guangdong Pharmaceutical University , Guangzhou , P.R. China.
authors.forename: Yun-Ming
authors.initials: YM
authors.lastname: Zhong
authors.affiliation: a School of Pharmacy , Guangdong Pharmaceutical University , Guangzhou , P.R. China.
authors.forename: Xuan-Ge
authors.initials: XG
authors.lastname: Cheng
authors.affiliation: a School of Pharmacy , Guangdong Pharmaceutical University , Guangzhou , P.R. China.
authors.forename: Mei-Feng
authors.initials: MF
authors.lastname: Cen
authors.affiliation: a School of Pharmacy , Guangdong Pharmaceutical University , Guangzhou , P.R. China.
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Wang
authors.affiliation: a School of Pharmacy , Guangdong Pharmaceutical University , Guangzhou , P.R. China.
authors.forename: Lin-Quan
authors.initials: LQ
authors.lastname: Zang
authors.affiliation: a School of Pharmacy , Guangdong Pharmaceutical University , Guangzhou , P.R. China.
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D002951:Citrates / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004058:Diffusion; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D016014:Linear Models; D061985:Madin Darby Canine Kidney Cells; D010539:Permeability; D011807:Quinolizines / Q000378:metabolism*; D065608:Renal Reabsorption / Q000187:drug effects; D000077559:Sodium Citrate; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D013696:Temperature; D000093842:Matrines
chemical_list: D000470:Alkaloids; D002951:Citrates; D016572:Cyclosporine; D003840:Deoxycholic Acid; D011807:Quinolizines; D000077559:Sodium Citrate; D012967:Sodium Dodecyl Sulfate; D013501:Surface-Active Agents; C037573:oxymatrine; D000093842:Matrines
keywords: Absorption enhancers; LC–MS; MDCK cells; passive transport