Effect of extract method on pharmacokinetics of baicalin and berberine in dogs

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7. J. 54-66. 2009 305 351-353. 12Yu LBridgers APolli Jet al. Vitamin E-TPGS increases ab- 8. sorption flux of an HIV protease inhibitor by enhancing its solubility and permeability J. J Pharm J. 2007234 270-272. Sci1999161812-1817. 9Cornaire G. Woodley JHermann P et al. Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo J. Int J Pharm2004278119-131. 10Wandel CKim R BStein C Met al. " Inactive" excipients such as Cremophor can affect in vivo drug disposition J. Clin Pharmacol Ther200373394-396. 11Wang ZRavula RCao Met al. Transporter-mediated multidrug resistance and its modulation by Chinese medicines and other herbal products J. Curr Drug Discov Technol20107 1 13Vautier SFernandez C. ABCB1the role in Parkinson's disease and pharmacokinetics of antiparkinsonian drugs J. Expert Opin Drug Metab Toxicol2009511 1349-58. 14Haber B AMohn K LDiamond R Het al. Induction patterns of 70 genes during nine days after hepaterctomy define the temporal course of liver regeneration J. J Clin Invest 199391 1319-1323. 15. Caco-2 J. 2007386 836-837. 1 2 1 1. 1500762. 150076 T S 1 S 2 Baicalin Ba Berberine Be T S 1 S 2 C max 7. 588 ± 0. 797ng /mlt Ba 7. 204 ± 1. 368ng /mls 1 Ba 0. 323 ± 0. 036ng /mlt Be 2. 044 ± 0. 653ng /mls 2 Bet max 8. 333 ± 1. 506hT Ba 8. 066 ± 0. 860hS 1 Ba 1. 750 ± 0. 274hT Be 2. 932 ± 0. 532hS 2 Be AUC 0 ~ 268. 7 ± 55. 97ng /h ml T Ba 218. 2 ± 77. 3ng /h ml S 1 Ba 2. 098 ± 0. 532ng /h ml T Be15. 232 ± 8. 36ng /h ml S 2 Be R969. 1 A 1001-1528201108-1326-04 Effect of extract method on pharmacokinetics of baicalin and berberine in dogs WANG Li 1 2 ZHAO Ying 1 1. Heilongjiang University of Traditional Chinese MedicineHarbin 150040 China2. School of Pharmacy Harbin University of Commerce Harbin 150076 China ABSTRACTAIM To investigate the effect of extract method on pharmacokinetics in dogs of baicalin Ba berberinebeby determining Ba and Be concentration of serum after administration of traditional Chinese medicine Gegen Qinlian Decoction T Scutellaria baicalensis Georgi DecoctionS 1 and Coptis chinensis Franch. DecoctionS 2. METHODS HPLC method was established to determine serum concentration of Ba Be and pharmacokinetic parameters were calculated. RESULTS The parameters in dogs after administration of T S 1 S 2. were as followsc max was 7. 588 ± 0. 797ng /mlt Ba 7. 204 ± 1. 368ng /mls 1 Ba 0. 323 ± 0. 036ng /mlt Be 2. 044 ± 1326 2010-09-15 LBH-Z08003 D200916 1975 Tel 045184838207E-mailkurb@ sohu. com

0. 653ng /mls 2 Bet max 8. 333 ± 1. 506hT Ba 8. 066 ± 0. 860hS 1 Ba 1. 750 ± 0. 274hT Be 2. 932 ± 0. 532hS 2 Be AUC 0 ~ 268. 7 ± 55. 97ng /h ml T Ba 218. 2 ± 77. 3ng /h ml S 1 Ba 2. 098 ± 0. 532ng /h ml T Be15. 232 ± 8. 36ng /h mlrespectively. CONCLUSION Extract method has significant effect on pharmacokinetic parameters of Ba and Be in dogs. KEY WORDSGegen Qinlian Decoctionbaicalinberberinedogs pharmacokinetics 9-12 2. 1 Ultimate TM C 18 250 mm 4. 6 mm 5 μm 1-4 30 1. 0 ml /min 20μL 5-6 - 0. 2% NaH 2 PO 4 7 ph 3. 0 48 52 V /V 280 nm - NaH 2 PO 4 ph 8 3. 0 40 60 V /V 346 nm 2. 2 18 3 6 1 1. 1 Dionex P680 TCC-100 Chromeleon ASI-100 UVD-340U -25 XKG6-A 2. 3 TGL-16G 1. 5 ml 1. 2 50 200 μl A0016 15 000 r /min 10 min 20 A0151 μl 2. 4 2. 4. 1 7. 8 min 9. 7 1. 3 min 6. 8 min T 11. 4 min 15 g 9 g 6 g5 2 000 ml 30 min2 200 ml 9 g 20 min 1 000 ml2. 4. 2 S 1 S 2 45 g 60% 10 ml 30 min2 1 000 0. 5 mg /ml ml 200 ml 1. 4 18 14 ± 2. 1kg 2 12 h T S 1 S 2 200 ml 195 g 1 2 4 6 8 10 12 16 20 24 36 h 5 ml 20 μl 2 min 5 ml 5 min 3 500 r /min 10 min 4 ml 1 5. 0 mg 4. 0 0. 4 mg /ml 0. 004 0. 01 0. 02 0. 04 0. 1 0. 2 mg /ml 0. 2 0. 5 2 5 20 50 μg /ml 100μL7 1327

1 2 1 Tab. 1 n = 5 Precision and method recovery of HPLC method to determine Ba in dog s serum n = 5 /% RSD /% /μg /ml 1 2 3 4 5 0. 05 94. 8 103. 1 94. 2 93. 2 107. 3 6. 4 1 95. 7 94. 5 103. 2 94. 3 105. 4 5. 3 4 98. 9 97. 2 105. 8 102. 8 95. 6 4. 2 0. 05 95. 2 96. 4 104. 2 109. 9 103. 1 5. 9 1 102. 2 104. 8 95. 5 96. 7 103. 7 4. 2 4 103. 2 94. 8 102. 4 97. 1 98. 7 3. 6 1 Fig. 1 HPLC HPLC chromatograms of Ba Be in serum A. B. 1. 2. C. 1. 2. D. S 1 1. E. S 2 1. F. T 1. 2. A. blank serum B. blank serum spiked with Ba and internal standard 1. Ba 2. Metronidazole C. blank serum spiked with Be and internal standard 1. Be 2. Lacidipine D. serum sample after administration of decoction S 1 to dogs 1. Ba E. serum sample after administration of decoction S 2 to dogs 1. Be F. serum sample after administration of decoction T to dogs 1. Ba 2. Be 10μL 0. 501 1. 317 5. 42 μg /ml 0. 492 1. 011 10 μl 1. 0μg /ml 2 4. 91 μg /ml 2. 3 min 0. 4 1 2 4 10 6 h-20 15d 3 20μg /ml RE% 12% 0. 02 0. 05 0. 20 0. 50 2. 00 5. 00 μg /ml 2. 4 2. 5 - T S 1 S 2 Ar /Ai C - 2 3 W = 1 /C 2 13 Ar / Ai = 12 196C - 31 153. 2 r = 0. 998 0 Ar /Ai = 0. 472C + 0. 021 6 r = 0. 998 3 0. 4 ~ 20 μg /ml 0. 02 ~ 5. 00 2 Tab. 2 n = 5 Precision and method recovery of HPLC method to determine Be in dog s serum n = 5 /% RSD /% /μg /ml 1 2 3 4 5 0. 05 94. 8 103. 1 94. 2 93. 2 107. 3 6. 4 1 95. 7 94. 5 103. 2 94. 3 105. 4 5. 3 4 98. 9 97. 2 105. 8 102. 8 95. 6 4. 2 0. 05 95. 2 96. 4 104. 2 109. 9 103. 1 5. 9 1 102. 2 104. 8 95. 5 96. 7 103. 7 4. 2 4 103. 2 94. 8 102. 4 97. 1 98. 7 3. 6 95% ~ 105% RSD < 10% 2. 4. 4 200 μl 3 μg /ml 2 T S 1-2. 4. 3 Fig. 2 Mean serum concentration-time curve of Ba after 3 0. 5 2. 5 15μg /ml administration of decoction T and S 1 to dogs 0. 05 1 4μg /ml 5 3 d 2. 6 RSD TS 1 S 2 DAS2. 0 1328

Fig. 3 3 Mean serum concentration-time curve of Be after administration of decoction T and S 2 to dogs C max t max λ Z - t 1 /2 - AUC 0 ~ t AUC 0 ~ = AUC 0 ~ t + C t /λ Z SPSS16. 0 3 4 3 Tab. 3 4 Tab. 4 n = 6 x ± s Parameters of Ba in dogs after administration of decoction T and S 1 n = 6 x ± s λ Z h - 1 0. 112 ± 0. 532 0. 099 ± 0. 035 C max ng ml - 1 7. 204 ± 1. 368 7. 588 ± 0. 797 t max h 8. 066 ± 0. 860 8. 333 ± 1. 506 t 1 /2 h 6. 215 ± 1. 706 7. 604 ± 2. 242 * MRT 0-36 h 21. 65 ± 3. 5 21. 00 ± 13. 07 MAT 0-36 h 13. 54 ± 13. 99 15. 51 ± 19. 61 AUC 0-36 ng h ml - 1 205. 7 ± 21. 9 223. 3 ± 42. 8 * AUC 0- ng h ml - 1 218. 2 ± 77. 3 268. 7 ± 55. 97 * * T P < 0. 05 n = 6 x ± s Parameters of Be in dogs after administration of decoction T and S 2 n = 6 x ± s J. 2006 34 81109- λ Z h - 1 0. 153 ± 0. 032 0. 134 ± 1. 56 1112. C max ng ml - 1 0. 323 ± 0. 036 2. 044 ± 0. 653 * 6. 7 t max h 1. 750 ± 0. 274 2. 932 ± 0. 532 * J. 2008 255 417-418. t 1 /2 h 3. 085 ± 1. 206 3. 75 ± 1. 75 7. MRT 0-36 h 5. 178 ± 1. 008 5. 132 ± 0. 141 MAT 0-36 h 0. 759 ± 0. 146 2. 355 ± 0. 156 * J. 2003 94 80-84. AUC 0-36 ng h ml - 1 1. 839 ± 0. 452 14. 90 ± 3. 47 * 8. AUC 0- ng h ml - 1 2. 098 ± 0. 532 15. 232 ± 8. 36 * J. 2010 329 1507-1510. * T P < 0. 05 3 S 1 T 1. 25 S 2 T 1. 52 S 1 T AUC T S 2 AUC 7 C max 5. 3 T S 2-1. J. 1991 4250. 2. J. 2008 39 560-562. 3. J. 2010335 785-788. 4. J. 2008 1705763. 5. 9. J. 2008 33222687-2691. 10. RP-HPLC J. 2003 263 50-53. 11. J 2005 116 29. 1. 1 12. 1329

J. 200634 13. 8 1109-1112. J. 1996 165 343-346. 1 1* 2 1. 1001022. 100190 Franz 28 h 35. 904 2 mg 75. 540 7 % 2. 457 7 mg 79. 955 7 % Franz R944. 2 + 7 A 1001-1528201108-1330-04 Study on eugenol and cinnamaldehyde's permeative properties of Erxiekang Emplastra in vitro YIN Xing-bin 1 NI Jian 1* SHEN Xiao-chun 2 1. Beijing University of Chinese MedicineBeijing 100190China2. Patent Examination Cooperation Center of SIPOBeijing 100102China KEY WORDSErxiekang EmplastraeugenolcinnamaldehydeFranz diffusion cell TK-6A YP 10002 1-2 110725-200610 110710-200714 20080402 20080403 20080404 SD 180 ~ 200 g SCXK2007-0001 2 2. 1 GC Franz 2. 1. 1 5 ml 1 ml 4. 862 0 mg 1 Agilent 6890 5 ml 2010-10-28 1985 Tel 01084738607 E-mailyxbtcm@ 163. com * E-mailnjtcm@ 263. net 1330