94 2 3 3. 53002 2. 53000 3. 543000 86. 2 mg kg -. 8 mg kg - R Rg Rb 3P97 AUC 0 - R Rg Rb R 0. 8 ± 0. 09 vs 0. 6 ± 0. 06 h Rg 2. 03 ± 0. 76 vs. 74 ± 0. 27 h Rb 0. 76 ± 0. 39 vs 0. 74 ± 0. 7 h R 0. 96 ± 0. 6 vs 0. 50 ± 0. h Rg 0. 87 ± 0. 05 vs 0. 02 ± 0. 0 h Rb 0. 92 ± 0. 2 vs 0. 44 ± 0. 07 h 3 248. 4% 07. 9% 52. 94% 55. 3% AUC 0 t 39. 7 ± 3. 89 vs 46. 9 ± 3. 86 mg L - h Lag 0. 45 ± 0. 8 vs 0. 92 ± 0. 3 h t max 0. 74 ± 0. 7 vs 0. 77 ± 0. 3 h Cl 3. 84 ± 0. 24 vs. 84 ± 0. 97 L kg - h - R969. R285 DOI 0. 3867 /j. issn. 000-3002. 202. 0. 09 A 000-3002 202 0-0094-05 Panax notoginseng saponins icariin 0737-20043 R 20004 Rb Rg Fisher Scientific Tedia 2-3. 2 8 ~ 0 kg Rb 0703-200424 SCXK 2008-0007. 3 LC-0AT SPD-0A. R 0745-20045 Sartorius BS224S DT-230A SK- Rg 0704-20038 TGL-6G-A 0AS-2 0932049 200GXNSFB03068. 4 986-956 - 6 2 3 E-mail hgliu @ 263. net Tel 077 5358272 2 h 3 R Rg Rb
95 8. 2 46. 8 3. 5 mg kg - Rb ω j = AUC j0 / AUC 0 20 R Rg Rb R 0. 5 57. 9 43. 4 mg kg - Rb AUC 0 = AUC R 0 + AUC Rg 0 + AUC Rb 0 R 0. 5. 5 2 2. 5 3 3. 5 4 6 8 h 4 ml Eppendorf ep C T = ω R C R + ω Rg C Rg + ω Rb C Rb 2 800 g 0 min 7 d. 5-20. 5. R 2. 4 mg Rb 3. 6 mg Rg 2 9. 2 mg 0 ml 237. 3 363. 97. 5 mg L - 2.. 8 mg 2.. 00 ml. 5. 2 R Rg Rb 2 ml 20 μl 2. 5 3. 7 2. 0 internal standard IS 8 mg L - 7. 5 min = 6 ml 2 min 800 g 0 min ep 40 0. 20 ml min 800 g 0 min. 5. 3 Welchrom-C8 4. 6 mm 250 mm 5 μm - 0 min V /V 2 79 ~ 5 min V /V 40 60 ~ 8 min V /V 45 55 ~ 20 min V /V 2 79 ~ 25 min V /V 2 79. 0 ml min - 20 μl 203 nm 30. 5. 4 40 0. 2 ml Fig. Chromatograms of Panax notoginseng saponins. 5. 2 by HPLC. A blank plasma B plasma spiked with R R Rg Rb Rg icariin and Rb. 4. 4 3. 6 and 3. 2 mg L - standard C j R Rb Rg ω j AUC 3 AUC C T plasma sample of enteric-coated capsules in dogs after po 86. 2 mg kg - for. 5 h. notoginsenoside R 2 ginsenoside Rg 3 icariin. 6 area under curve AUC 4 ginsenoside Rb. 4 ω j - 2.. 2 3P97 R Rb R Rg Rb Rg AUC 0 3 Y = 22. 266X - 2. 473 r = 0. 998 Y = 24. 95X - AUC 0 30. 463 r = 0. 9965 Y = 3. 886X - 4. 5 r = ω j 3 0. 9983 R Rg Rb. 0 ~ 79. mg L - 0. 9 ~ 90. 9 mg L - 0. 9 ~ 9. 8 mg L - 0. 0. 2 0. 2 mg L - 0. 3 0. 4 0. 4 mg L -
96 2.. 3 R Rg Rb 50% RSD 2. 0% RSD 3. 0% 24 h 5 4 RSD <. 9% Tab. Method recovery and extraction recovery of HPLC 2. 2 assay Drug / Method recovery / mg L - % Extraction recovery / % R 5. 93 89. 0 ± 2. 5 7. 3 ± 2. 2 23. 73 90. 9 ± 3. 6 86. 7 ±. 6 8. 60 03. 4 ± 5. 77. 3 ± 2. Rg 6. 82 87. 9 ± 4. 3 72. 2 ± 3. 7 68. 8 92. 2 ±. 3 88. 5 ± 3. 7 36. 32 88. 8 ± 3. 2 79. ± 2. 6 Rb 4. 59 95. 8 ± 3. 3 67. 6 ± 4. 8 9. 76 89. 6 ± 2. 3 88. 6 ± 5. 83. 52 04. ± 4. 2 90. 6 ± 6. 4 珋 x ± s n = 5. 2.. 4 R Rg Rb - 2 3P97 SUM Akaike AIC r 2 /C 2 2 R Rb Rg AUC 248. 4% 07. 9% 52. 94% 55. 3% - AUC 0 - ω j 3 Fig. 2 Plasma concentration-time profiles of after enteric-coated capsules and capsule given to Beagle dogs. A notoginsenoside R B ginsenoside Rg C ginsenoside Rb D plasma concentration-time profiles of after integration. x 珋 ± s n = 6.
97 Tab. 2 Main pharmacokinetic parameters of enteric-coated capsules and capsule in dogs Parameter R Rb Rg Ka /h - 24. 04 ± 2. 34 27. 20 ± 2. 45 2. 42 ± 0. 8. 99 ± 0. 5 0. 90 ± 0. 8 0. 58 ± 0. 06 Lag time /h 0. 50 ± 0. 0. 96 ± 0. 6 0. 92 ± 0. 2 0. 44 ± 0. 07 0. 02 ± 0. 0 0. 87 ± 0. 05 t /2 ka /h 0. 03 ± 0. 0 0. 02 ± 0. 0 0. 29 ± 0. 9 0. 35 ± 0. 09 0. 77 ± 0. 28. 20 ± 0. 69 t /2 ke /h. 35 ± 0. 34 3. 5 ± 0. 2. ± 0. 8 0. 80 ± 0. 4 2. 03 ± 0. 65. 67 ± 0. 76 t max /h 0. 6 ± 0. 06 0. 8 ± 0. 09 0. 76 ± 0. 39 0. 74 ± 0. 7. 74 ± 0. 27 2. 03 ± 0. 76 c max /mg L - 2. 2 ± 0. 37. 0 ± 0. 27 22. 60 ± 0. 89 23. 96 ± 2. 73 3. 35 ± 0. 76 2. 75 ± 0. 45 AUC 0 t /mg L - h 2. 48 ± 0. 89 4. 77 ±. 09 58. ± 4. 76 52. 38 ± 5. 78 7. 76 ± 2. 3 5. 38 ±. 89 Cl /L kg - h - 2. 34 ± 0. 00. 70 ± 0. 23 0. 54 ± 0. 09 0. 83 ± 0. 2 3. 26 ± 0. 45 3. 04 ± 0. 69 V /L kg - 4. 56 ± 0. 67 7. 70 ± 0. 73 0. 87 ± 0. 4 0. 95 ± 0. 6 9. 53 ±. 08 7. 32 ±. 09 Ka absorption rate constant Lag time absorption lag time t /2 ka absorption half life t /2 ke eliminate half life t max peak time c max maximum plasma concentration AUC 0 t the area under the concentration-time curve Cl clearance V apparent volume of distribution. 珋 x ± s n = 6. Tab. 3 Main pharmacokinetic parameters of entericcoated capsule and capsule in dogs after the integration of blood concentration based on AUC 0 Parameter Ka /h - 2. 50 ± 0. 43 2. 20 ± 0. 65 Lag time /h 0. 92 ± 0. 3 0. 45 ± 0. 8 t /2 ka /h 0. 28 ± 0. 04 0. 32 ± 0. 07 t /2 ke /h. 22 ± 0. 24 0. 93 ± 0. 25 t max /h 0. 77 ± 0. 3 0. 74 ± 0. 7 c max /mg L - 7. 27 ±. 87 6. 74 ± 2. 76 AUC 0 t /mg L - h 46. 9 ± 3. 86 39. 7 ± 3. 89 Cl /L kg - h -. 84 ± 0. 97 2. 84 ± 0. 28 V /L kg - 3. 23 ± 0. 39 3. 84 ± 0. 24 See Tab. 2 for the lengend. 珋 x ± s n = 6. 3 AUC 0 4 6 AUC 0 7 RP- HPLC Zhang JF Zhang DF. Study advancement in pharmalcological actions of total saponins of Panax notoginseseng J. Med Recapit 2007 3 6 472-474. 2 Li XY Hao HP Wang GJ Sun JG Liang Y Xie L 3 et al. Integrated pharmacokinetic study of multiple effective components contained in total Panax notoginsenoside J. Chin Nat Med 2008 6 5 377-38. 3 R Rb 3 Wang Y Liu TH Wang W Wang BX. Research on Rg the transformation of ginsenoside Rg by intestinal flora J. China J Chin Mater Med
98 200 26 3 88-90. 4 Hasegawa H Sung JH Matsumiya S Uchiyama M. Main ginseng saponin metabolites formed by intestinal bacteria J. Planta Med 996 62 5 453-457. 5 Yu ZG. Establish and validate biopharmarceutical analysis method M Li HZ. Biopharmarceutical Analysis. Beijing China Medical Science Press 2003 30. 6 Han M. Studies on oral absorption of Panax notoginsenoside and preparation of W /O microemulsion for oral administration D. Shanghai Fudan University 2006. 7 Feng L Jiang XH Zhou J Yang JY. Studies on absorption kinetics of sanchinoside R and ginsenoside Rg in rat intestine J. Chin Pharm J 2006 4 4 097-02. Pharmacokinetics of Panax notoginseng saponins enteric-coated capsules in Beagle dogs QIN Yan-e LIU Hua-gang LAI Ling LU Shi-hua WEN Li 2 CHEN Ming 3 LIU Guan-ping 3. Pharmacy School Guangxi Medical University Nanning 53002 China 2. Guangxi Traditional Chinese Medical University Nanning 53000 China 3. Guangxi Wuzhou Pharmaceutical Group Co. Ltd. Wuzhou 543000 China Abstract OBJECTIVE To investigate pharmacokinetics of Panax notoginseng saponins in Beagle dogs. METHODS enteric-coated capsules 86. 2 mg kg - and capsules. 8 mg kg - were administered to dogs according to an open randomized crossover design. The plasma concentration of notoginsenoside R ginsenoside Rg and Rb was determined by RP-HPLC. Pharmacokinetic parameters were calculated by 3P97 software so were those after the integration of blood concentration based on AUC 0. RESULTS Compared with reference preparation t max of test preparation R Rg Rb increased 0. 8 ± 0. 09 vs 0. 6 ± 0. 06 h for R 2. 03 ± 0. 76 vs. 74 ± 0. 27 h for Rg 0. 76 ± 0. 39 vs 0. 74 ± 0. 7 h for Rb Lag times were prolonged 0. 96 ± 0. 6 vs 0. 50 ± 0. h for R 0. 87 ± 0. 05 vs 0. 02 ± 0. 0 h for Rg 0. 92 ± 0. 2 vs 0. 44 ± 0. 07 h for Rb. The relative bioavailability of R Rg Rb and was 248. 4% 07. 9% 52. 94% and 55. 3% respectively. After integration the main pharmacokinetic parameters of capsules and enteric-coated capsules respectively were AUC 0 t 39. 7 ± 3. 89 vs 46. 9 ± 3. 86 mg L - h Lag times 0. 45 ± 0. 8 vs 0. 93 ± 0. 3 h t max 0. 74 ± 0. 7 vs 0. 77 ± 0. 3 h Cl 3. 84 ± 0. 24 vs. 84 ± 0. 97 L kg - h -. CONCLUSION enteric-coated capsule can improve the oral bioavailability of. Key words pharmacokinetics Panax notoginseng saponins Beagle dogs plasma drug concentration Foundation item The project supported by Corporation Technologically Commissioner Foundation of Guangxi Zhuang Autonomuous Region 0932049 and Natural Science Foundation of Guangxi Zhuang Autonomuous Region 200GXNSFB03068 Corresponding author LIU Hua-gang E-mail hgliu@ 263. net Tel 077 5358272 20-05-28 20--9