Pharmacokinetic stud ied on berber ine hydrochlor ide in Rh izoma Coptidis - Fructus Evodiae drug - pa ir in rat
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1 Chin J Pharm Anal 2009, 29 (5) 755,, 3 (, ) : -,,, :,: D iamonsil C 18 (150 mm 416 mm, 5m) ;: moll - 1 ( ) ; : 110 mlm in - 1 ; : 345 nm; : 35 : : MRT 024 = ( ) h, MRT 0 = ( ) h, AUC 024 = ( ) mg(lh) - 1, AUC 0 = ( ) mg(lh) - 1, T max = ( ) h, C max = ( ) mgl - 1 ; :MRT 024 = ( ) h,mrt 0 ( ) h, AUC 024 = ( ) mg(lh) - 1, AUC 0 = ( ) mg(lh) - 1, T max = ( ) h, C max = ( ) mgl - 1 ; :MRT 024 = ( ) h,mrt 0 = ( ) h, AUC 024 = ( ) mg(lh) - 1, AUC 0 = ( ) mg(lh) - 1, T max = ( ) h, C max = ( ) mgl - 1 :,,, : ;;; : R917 : A : (2009) Pharmacokinetic stud ied on berber ine hydrochlor ide in Rh izoma Coptidis - Fructus Evodiae drug - pa ir in rat WANG J ing, YUAN Zi - m in, ZHANG Zhen - qiu 3 ( School of Pharmacy, L iaoning University of TCM, Dalian , China) AbstractO bjective: To study the pharmacokinetics of berberine hydrochloride in rat p lasma after oral adm inistra2 tion separately to the monomer of berberine hydrochloride, the extracts of Rhizoma Cop tidis and drug - pair of Rhi2 zoma Cop tidis - Fructus Evodiae containing equal quantity of berberine hydrochloride, to compare the differences and exp lore the pharmacokinetics effection on berberine hydrochloride in rat p lasma after oral adm inistration sepa2 rately to Rhizoma Cop tidis and drug - pair. M ethod: HPLC was used to determ ine the quantity of berberine hydro2 chloride in rat p lasma. A D iamonsil C 18 (150 mm 416 mm, 5m) column was used, the mobile phase consisted of acetonitrile, methanol and 0105 moll - 1 potassium dihydrogen phosphate ( ), the flow rate was 110 ml m in - 1, the UV detector was operated at 345 nm and the column temperature was controlled at 35. Result: Phar2 macokinetic parameters of the momoner of berberine hydrochloride: MRT 024 = ( ) h, MRT 0 = ( ) h, AUC 024 = ( ) mg(l h) - 1, AUC 0 = ( ) mg (Lh) - 1, T max = ( ) h, C max = ( ) mgl - 1 ; Pharmacokinetic parameters of the extract of Rhizoma Cop tidis: MRT 024 = ( ) h, MRT 0 = ( ) h, AUC 024 = ( ) mg(lh) - 1, AUC 0 = ( ) mg(l h) - 1, T max = ( ) h, C max = ( ) mgl - 1 ; Pharmacokinetic parameters of the extract of drug - pair: MRT 024 = ( ) h, MRT 0 = ( ) h, AUC 024 = ( ) mg(l h) - 1, 3 Tel: (0411) ; E - mail: zhangzhenqiu@ sina. com
2 756 Chin J Pharm Anal 2009, 29 (5) AUC 0 = ( ) mg(lh) - 1, T max = ( ) h, C max = ( ) mgl - 1. Conclusion: Rhizoma Cop tidis and drug - pair both enhance the absorp tion and elim ination of berberine hydrochlo2 ride. By the analysis of compartment model, they are all one - compartment model, they have no significant effect on their distribution from the centre compartment to the periphenal compartment. Key words: Rhizoma Cop tidis; Fructus Evodiae; berberine hydrochloride; pharmacokinetic,,,,,88gml - 1,-,,,, -, - 6 1,,, - 6 1, m in, rm in m in,,,, 40,50L,20L (,, ) ( ) ; L,,, ; 100 L, ,, 01011, 01022, 01044, gml - 1 Coptis chinensis Franch., 312,, ( X ), Evodia rutaecarpa (Juss. ) Benth. ( Y),(1 C - 2 ) SD,, g, 112 LC - 10ATvp, SPD - 10Avp ( ) ; TGL - 16G ( ), XW - 80A ( ) 2,: Y = 81560X r = gmL - 1, 01002gmL L, , 01022, 01088gmL - 1, : D iamonsil C 18 ( 150 mm 416 mm, 5 6, 200L, 312 m) ;: moll - 1 ( ) ; : 110 ml m in - 1 ; : 345nm; : ,, , 01022, 01044, 01088, 01176gmL - 1, , 240gmL ml50 ml,, 1147gmL - 1, L,510 ml, 50 L, 1 mol L L 210 ml, 2,, 100L (3), 40,50L,
3 Chin J Pharm Anal 2009, 29 (5) Fig 1HPLC chromatogram s of berberine hydrochloride and nitidine chloride ( internal standard) in rat p lasma A. ( blank p lasma) B. + ( ) +( gml - 1 ) [ blank p lasma sp iked with internal standard ( nitidine chloride) and berberine hydrochloride (01044gmL - 1 ) ] C. 1 h( p lasma samp le 1 h after ig. berberine hydrochloride to a rat) D. 1 h(p lasma samp le 1 h after ig. Rhizoma Cop tidis extracts to a rat) E. 1 h(p lasma samp le 1 h after ig. drug - pair extracts to a rat) 1. ( berberine hydrochloride) 2. ( nitidine chloride) 1 m in, rm in m in20l HPLC, ( 3 ) 2,, 3 ( ) %, ( ) %, ( ) %( ) % , 01022, gml - 1, 6, 3 d,,,, RSD 714%, 611%, 510% ; RSD 517%, 510%, 415% ; 9318%, 10717%, 9911% , 01022, gml - 1 6, (20 ) 1 d, 3 ( RE) 3 RE %, 717 %, %, 1 d, 4 411, 10 65%, 115 h, 3,,,, 412- (6 1) 6 1, 10 65%, 115 h, 3,,,, 413 3,24 h,, 015 ml, 1 kg g, 1 kg g 411, 1 kg g 412, 0125, 015, 0175, 1, 2, 3, 4, 6, 8, 12, 24 h 015 ml,, r min min, 200L 50L, 1 moll L, 312, 414-2,,DAS 210,1
4 758 Chin J Pharm Anal 2009, 29 (5) 2( n = 6) Fig 2Mean p lasma concentration - time curves of berberine hydrochloride A. ( berberine hydrochloride) B. ( extract of Rhizoma Cop tidis) C. - ( extract of Rhizoma Cop tidis and Fructus Evodiate drug - pair) 1 ( SD, n = 6) Tab 1Pharmacok inetic param eters of berber ine hydrochlor ide in ra ts after ora l adm in istra tion separa tely to the m om oner of berber ine hydrochlor ide, the extracts of Rh izoma Coptid is and drug - pa ir ( m ean SD, n = 6) (parameter) ( ig. the extract of berberine hydrochloride to rats) ( ig. the extract of Rhizoma Cop tidis to rats) ( ig. the extract of drug - pair to rats) MRT 024 /h MRT 0 /h AUC 024 /mg(l h) - 1 AUC 0 /mg(l h) T max /h C max /mgl , T max [ ( ) h ], C max [ ( ) mgl - 1 ]; T max [ ( ) h ] T max [ ( ) h ], C max (mgl - 1 ), MRT 0 [ ( ) h ] MRT 0 [ ( ) h) ] MRT 0 [ ( ) h ],,,,,, ;,,,,,, DAS 210,,, [ 13 ], -,,,,,,,, C 18, [ 46 ], moll - 1 ( ),,, 1 Hua W, D ing L, Chen Y, et al. Determ ination of berberine in human p lasma by liquid chromatography - electrospray ionization - mass
5 Chin J Pharm Anal 2009, 29 (5) 759 spectrometry. J Pharm B iom ed Anal, 2007, 44 (4) : 931 2Deng YX, Lu T, Xie L, et al. H igh - performance liquid chromato2 graphic method for the determ ination and pharmacokinetic study of wogonoside in rat serum after oral adm inistration of traditional Chi2 nese medicinal p reparation Huang - L ian - Jie - Du decoction. B i2 om ed Chrom atogr, 2006, 20 (10) : L i Y, Gao JP, Xu X, et al. Simultaneous determ ination of baicalin, rhein and berberine in rat p lasma by column - switching high - per2 formance liquid chromatography. J Chrom atogr B Analyt Technol B i2 om ed L ife Sci, 2006, 838 (1) : 50 4ZHONG Da - fang (). Some aspects in establishing standard curves in bioanalyseswith the weighted least squaresmethod ( ). Chin J Pharm Anal( ), 1996, 16 (5) : 343 5L IU L i( ), DENG Yuan - xiong (), ZHANG Dong - mei (), et al. Effect of berberine on pharmacokinetics of baicalin in rats(). Chin J N at M ed ( ), 2007, 5 (2) : 137 6Tan B,Ma Y M, Shi R, et al. Simultaneous quantification of three al2 kaloids of Cop tidis Rhizoma in rat urine by high - performance liquid chromatography: app lication to pharmacokinetic study. B iopharm D rug D ispos, 2007, 28 (9) : 511 ( ) 3 3, () (), ; ;,,,"", 4,, http: / /www. nicpbp. org. cn
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