马兜铃酸I在大鼠体内的代谢特征研究.pdf-道客多多

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1、 . Iv 8 =+苏null 涛1, 屈null 磊1, 张春丽2,蔡少青3, 李晓玫1(1.北京大学第一医院肾内科, 北京100034; 2.北京大学第一医院核医学科, 北京100034;3.北京大学药学院, 北京100038)K1 null “: g . I(AAnullI)v 8 =0 +bZE:125IS:AAnullIT U64,v BQ g1 !Y X410 gnullkg- 1125IS:AAnullI(cAAnullI37. 2mgnullL- 1)0A, 125InullAAnullIi# q,3P87 Ei9 0 b Ha /9# 125InullAAnullIc,9 I

2、D%as1,4 S HW M,s1 AAnullI# s+bT:v BQ g1 !Y X4,AAnullI l ,30 minr,1.5 h, iv,24 hi ,010 d H68. 9%AAnullI Tib E +50= i , A U: gAAnullI0.74 hr(Tmax),r i( Cmax)0.92 mgnullL- 1,s ( t1/2null)0.68 h,h“ ( t1/2null) 20. 46 h,V4s ( V/F)87.39 mL,9 b“ qCL(s) 5.85 mLnullh- 1( 0.10 mLnullmin- 1)b0AAnullI s 7AAnull

3、Ia /s19,#4 dr,7Q/; /#5? 6,4 (40 d)Kl, A # ( P98%bGF254Aa oTa ; )a=J+(DMSO) (1 k4 b1.2.2null1 !Y X4!1 !YAristolochiae manshuriensis Kom.,1 g B0K ,F0kb | a b 40 min,mX30 min,Q2Qb| X0AF inull676null29 7 2004 M7null null null null null null null null nullnull null null 中国中药杂志ChinaJournal of ChineseMater

4、iaMedicanull null null null null null nullVol. 29, Issue null 7July, 2004aV rc 3067 gnullL- 1 (AAnullIc 0. 1112mg),4 null i!b1.2.3null 125Inull . nullIS:#s 4Bnull null 125IS: oTES: |AAnullI 400 nullg,Nanull125I(17. 4 mCinullnullg- 1) 2 mCi0. 5 molnullL- 1 PBS(pH 7.0) ,F oT 10 mgnullL- 1Q3 4min, ; )Q

5、b ES:s 4B,9 125nullInullAAnullIS: q56.8%bK26.7 mCinullmL- 1125InullAAnullI A, bB100%,4 nullbQ i!b1.2.4null1 !Ynull125InullAAnullI0A!|!z1 !Y X43 mL,F 125InullAAnullI1 .067nullCi( 40nullL) ,1 !Y125InullAAnullI(0.356 nullCinullmL- 1) ,HPLCZEi9 cAAnullI0.1116 mgnullnullCi- 1,0. 1 mgnullnullCi- 1bS:AAnul

6、lI99. 64% , 125IS:AAnullI0.36%, i37.2 nullgnullmL- 1b1.3 null LZEv s2Fb1F27, J15 h,1 !Ynull125InullAAnullI0A(3 mL/)91Q,sY0 HW(5,10,15 min,0. 5,1, 1.5, 2,3,24 h) 3, 125InullAAnullIc #0 9 b 6BFv 42,E0,iv9) HW9 1 125InullAAnullIF h , HW(00.5,1,2,5,10 h, 1,2, 3,4, 5,9, 16,30, 40 d) 3,1Fv L ,AAnullI8 =s

7、4b1.3.1null) S = |Jv 1 |) , b 9 ,1 500 rnullmin- 1 15 min, =|4 null ib H = |aa aka /aa#v /vy F,!i s,sYb1.3.2null_S1.3.2.1null 125InullAAnullIc nullnullb f9 (FJ- 2008P) 100 nullLb 9 ( cpmnull100 nullL- 1),9 AAnullI i(nullgnullmL- 1)b1.3.2.2null AAnullI null HW 125InullAAnullI i (,3P870 ,i AIC( ES) 4K

8、D ,9 0 b1.3. 2.3null# 125InullAAnullIc nullnullb f9 (FJ2008- P) | B# 125InullAAnullIc ,# b 9 (cpmnullg- 1)V Ub9 # 125InullAAnullI ,sYID%( # b 9 g b 4 s )s1( # b 9 b 9 1)V Ub1.3.2.4null 125InullAAnullI qnull SephadexG- 50 1% d b1 2 h,0. 2molnullL- 1 PBS !b |F“ 800 1 000 nullL9b 9 “V, l“ 1 mL M 20z,sY

9、b 9 ,9 q,9 T M1cpm/“ 9cpm, %V Ub b 9 ( Mnb1.4nulld9) HW“ T (x null sV UbB HW# ,B# HWW1 FW_(SPSS 10.0d9 q) ,# FW1 ( SASd9 q), P 0. 05) ;,#125InullAAnullIs124 48 h A(P 0. 05)bnull nullm5A U s# 125InullAAnullIs124 h HW Mb Vn125InullAAnullI 01 2 d H # s1Xr K ,7 6bBM#CK*, /aka aa#, #CK,502, 4,40 d HCs1 6

10、b1 HW# s1Y Vn:02 d H,# # ,sY #3. 25,/#1. 41( P #,sY #3.062. 25( P 0. 05),7a /=WAs; 16 d H,# WAs;30, 40 d H, /#s1A # , n, 9sY24 ha4d 2.564. 96( P 0.05)b 6,#M t + y, 125InullAAnullIs2, 4? 6,16? HQ,Mb3null) null nullc . s0 / sa8 =T+ “5 5b . 0,ks . # 3a 3aaR #8a a /# # 1* P 0.05 ; # 1# P 0. 05 . “ - 1s

11、5bS =;sY / = AAnullIZE E AAN /#h 6,9, LAAnullI LAAN1 /0sBb3c . 01 !Yb S:AAnullIA,Q g0AAnullIv 8 =+ 4s, ZE 2,eL, ?sO 0g, b ?VAAnullI 9, T VVN 0sAAnullIv 8 =0 +b1 . 0 + . bS=;,s;E_v 8 =F . (AAnullI/II)s f ,?C 015 min,AAnullI/II /#sK, 7b= i ,9 h“ (T1/2null)34 min,V4s ( Vd) 202 mLnullkg- 1, b“ qClr 4 mL

12、nullmin- 1nullkg- 110b 7, 0oAAN g0M,yNBTK0 bS; Ev g00+,T?C, AAnullI, AAnullII gvs .=nullI, null(ALnullI,ALnullII) T,i VV Ua 11b_ZE K# C HW 4,T9EAA 0 YS Nb3K?C,sAANhT01 M = ?ALs;S T VP0i /Mh ?C /F ?AAnullDNAF12btT4 U,AA 0 F V ? T,i V ? /# ?b,3 nQ Q g0null679null29 7 2004 M7null null null null null nu

13、ll null null nullnull null null 中国中药杂志ChinaJournal of ChineseMateriaMedicanull null null null null null nullVol. 29, Issue null 7July, 200440 d0# s bTA U,AAnullI g ls ,010 d(12T1/2null) AAnullI q68. 9%,4U AAnullI V ? 8 =1br20.46 hh“ #5.85 mLnullh- 1 b“ q AAnullI 0,18 = b“d , T “50WV 0 HWV ( V ?/08 =

14、b g0 sah“ 1 0o, g0+,9 “5 c .0AANWa 07h 1CMbAAnullIs+s?C,AAnullI g Vs# , s 0.68 h, g90,#K = Kbv# FAAnullIc #s1 (24 48 h b048 h =,a# =125InullAAnullIs1 A/,4 UN W v AAnullI ?a UAa# b“b7# AAnullI9c / H, s1A 6, AAnullI_t# s t bBC /#l,04 9 d H /#s H n,730,40 d H /#125InullAAnullIs1V #7 B,B LAAnullI L /#s+

15、sbi ,#AAnullIs024hK7 6,2 9?B)K , v,V AAnullI#F F ,4 U V ?s# ,Dc . 09 V 13,14, N+M1)b ID1 null k ,null ,null,. !Y /l5W /h# “5h +s. = S, 2001, 40(10): 681.2 nullnull,:/G, null,. . /h “5h VC.D, 2001, 81(18): 1101.3 null Muniz Martinez M C, Nortier J, Vereerstraeten P, et al. Progressionrate of Chinese

16、herb nephropathy: impact of Aristolochia fangchi innullgested dose. Nephrol Dial Transplant, 2002, 17(3): 408.4 null Cosyns J P. Aristolochicacid andnull Chinese herbs nephropathynull : A renullview of the evidenceto date. DrugSaf, 2003, 26(1): 33.5 nullnull0, 5,y +,.01 !Y F ?s.D Sv, 2000, 32(1): 18

17、.6 null Cosyns J P, Dehoux J P, Guiot Y, et al. Chronic aristolochic acidtoxicity in rabbits: amodelofChineseherbs nephropathy? KidneyInt,2001, 59(6):2164. 7 null Nortier J L, Martinez M C, SchmeiserH H, et al. Urothelial carcinonullmaassociated with the use of a Chinese herb (aristolochia fangchi).

18、NewEnglJ Med, 2000, 342: 1686.8 null Vanherwegham J L, Depierreux M, Tielemans C, et al. Rapidly pronullgressive interstitial fibrosis in young women: association with slimmingregimen including Chinese herbs. Lancet, 1993, 341: 387.9 nullE ,fk , i,. . /h y # il.D, 2001, 81(18):1095.10 nullM. . c ,s;

19、E#0 .0, 1984, 19(3): 224.11 null Krumbiegel G, Hallensleben J, Mennicke W H. Studies on themetabolism of aristolochic acids I and II. Xenobiotica, 1987, 17(8): 981.12 null Schmeiser H H, Bieler C A, Wiessler M, et al. Detection of DNAadducts formed by aristolochic acid in renal tissue from patients

20、withChinese herbs nephropathy. Cancer Research, 1996, 56: 2025.13 null Levi M. Acute hepatitis in a patient using a Chinese herbal teanull acasereport. Pharm WorldSci, 1998, 20(1): 43.14 null Rossiello M R, Laconi E, Rao PM, et al. Induction ofhepatic nodnullules in the rat by aristolochic acid. Can

21、cer Lett, 1993, 71(1null3): 83.StudiesonpharmacodynamiccharacteristicsofaristolochicacidIinratsSU Tao1, QU Lei1, ZHANG Chunnullli2, CAI Shaonullqing3, LI Xiaonullmei1(1. RenalDivision, Peking University FirstHospital, Beijing 100034, China;2. Department of NuclearMedicine, Peking University FirstHos

22、pital, Beijing 100034, China;3. School of PharmaceuticalSciences, Peking University, Beijing 100034, China)Abstractnull Objective: To study pharmacodynamiccharacteristics by oral administration aristolochic acid I (AAnullI) in rats. Method:After onenulltimeoral administration of Aristolochiaemanshur

23、iensis decoction 10gnullkg- 1 and 125null I labeled AAnullI( containingAAnullI 37.2nullgnullmL- 1),null680null29 7 2004 M7null null null null null null null null nullnull null null 中国中药杂志ChinaJournal of ChineseMateriaMedicanull null null null null null nullVol. 29, Issue null 7July, 2004wholeblood c

24、oncentration of 125null InullAAnullI and the binding rateof serum albumin weredetected in 69 normal wistarmale rats. Metabolicdynamicparameters werecalculated by program 3P87with atwo compartment model. Thedistribution ratioand ID% of ninevisceraortissueweremeanullsured and comparedwith otheruntil t

25、he40th day. Result: After oral administration, AAnullIwas rapidly absorbed into the blood and reached itspeak at 30 minutes and lasted till 90 minutes. AAnullI concentration in the blood gradually declined afterwards. 24 hours later, only few AAnullIcould bedetected. By the10th day, 68.5% of AAnullI

26、 presented as the binding type with serum albumin. Pharmacodynamic parameters werecalculated as follows: Tmax 0.74 h, Cmax 0.92nullgnullmL- 1, t1/2null0.68 h, t1/2null20.46 h, V/F 87.39mL, CL( s) 5.85 mLnullh- 1( 0.10 mLnullmin- 1) . On theother hand, after oral administration AAnullIwas rapidly dis

27、tributed toall thevisceraortissue, whosepeak appeared in 5minnullutes and thevalleculawas from 24 to 48hours. The distribution ratio of AAnullIrosein thekidney after 24 hours, and it showed thehighest levelin thekidney and in the liver bythe4th day comparedwith otherorgans ortissue ( P 0. 05). Howev

28、er, thedistribution ratio of AAnullIin thekidney becamethemost dominant oneafterthe30th andthe40th daycomparedwith theothers( P 0.05). Conclusion: AAnullIis rapidly abnullsorbed after oral administration in rats. Its distribution hastheorgan specificity, which is characterized as thepossiblepartialm

29、etabolism in theliver andthe accumulation inthekidneybecauseof rather slower elimination. The characteristics maybe related tothe long term nephrotoxicityof AAnullI.Key wordsnull aristolochic acid I; pharmacokinetics; distribution; binding rateof serum albumin; kidney3 I null -|0 %BELnull74023T孙null

30、斌, 瞿伟菁* , 张晓玲, 杨煌建, 庄秀园, 章null 平(华东师范大学生命科学学院, 上海200062)K1 null “:)|0(STT)8 ! %BELnull74029T#TbZE:MTTSRBE_|0 %BELnull7402T, 4# T% (FCM)_ STT %BELnull7402r, T% _BELnull7402%Bclnull2VrbT: null STT ?4G %BELnull74029; null%AC M,FCMC; null STT ?BELnull7402%Bclnull2Vrb :STT8 ?BELnull7402%9i ?%, ToB /Bcln

32、2019# T,i) STT%T V ? b1 null ZE1.1null 1.1.1null%# !null %BELnull7402,1 S Z% 3 % o, !c10% l d b, 1 null 105 UnullL- 1 , 100 mgnullL- 1 RPMI1640(GIBCO) !,37 null ,5%CO2 !Q !b1.1.2 null k4N null: (MTT)1MERK;J1Amresco ; B(SRB)anull681null29 7 2004 M7null null null null null null null null nullnull null null 中国中药杂志ChinaJournal of ChineseMateriaMedicanull null null null null null nullVol. 29, Issue null 7July, 2004

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