PNS mg kg - 1. Rb 1

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1 mg kg -. 8 mg kg - R Rg Rb 3P97 AUC 0 - R Rg Rb R 0. 8 ± vs 0. 6 ± h Rg ± vs. 74 ± h Rb ± vs ± 0. 7 h R ± 0. 6 vs ± 0. h Rg ± vs ± 0. 0 h Rb ± 0. 2 vs ± h % 07. 9% % 55. 3% AUC 0 t ± vs ± mg L - h Lag ± 0. 8 vs ± 0. 3 h t max ± 0. 7 vs ± 0. 3 h Cl ± vs. 84 ± L kg - h - R969. R285 DOI /j. issn A Panax notoginseng saponins icariin R Rb Rg Fisher Scientific Tedia ~ 0 kg Rb SCXK LC-0AT SPD-0A. R Sartorius BS224S DT-230A SK- Rg TGL-6G-A 0AS GXNSFB net Tel h 3 R Rg Rb

2 mg kg - Rb ω j = AUC j0 / AUC 0 20 R Rg Rb R mg kg - Rb AUC 0 = AUC R 0 + AUC Rg 0 + AUC Rb 0 R h 4 ml Eppendorf ep C T = ω R C R + ω Rg C Rg + ω Rb C Rb g 0 min 7 d R 2. 4 mg Rb 3. 6 mg Rg mg 0 ml mg L mg ml R Rg Rb 2 ml 20 μl internal standard IS 8 mg L min = 6 ml 2 min 800 g 0 min ep ml min 800 g 0 min Welchrom-C mm 250 mm 5 μm - 0 min V /V 2 79 ~ 5 min V /V ~ 8 min V /V ~ 20 min V /V 2 79 ~ 25 min V /V ml min - 20 μl 203 nm ml Fig. Chromatograms of Panax notoginseng saponins by HPLC. A blank plasma B plasma spiked with R R Rg Rb Rg icariin and Rb 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 mg kg - for. 5 h. notoginsenoside R 2 ginsenoside Rg 3 icariin. 6 area under curve AUC 4 ginsenoside Rb. 4 ω j P97 R Rb R Rg Rb Rg AUC 0 3 Y = X r = Y = X - AUC r = Y = X r = ω j R Rg Rb. 0 ~ 79. mg L ~ mg L ~ 9. 8 mg L mg L mg L -

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 ± ± ± ± ± ± 2. Rg ± ± ± ± ± ± 2. 6 Rb ± ± ± ± ± ± 6. 4 珋 x ± s n = R Rg Rb - 2 3P97 SUM Akaike AIC r 2 /C 2 2 R Rb Rg AUC % 07. 9% % 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.

4 97 Tab. 2 Main pharmacokinetic parameters of enteric-coated capsules and capsule in dogs Parameter R Rb Rg Ka /h ± ± ± ± ± ± Lag time /h ± ± ± ± ± ± t /2 ka /h ± ± ± ± ± ± t /2 ke /h. 35 ± ± ± ± ± ± t max /h 0. 6 ± ± ± ± ± ± c max /mg L ± ± ± ± ± ± AUC 0 t /mg L - h ± ± ± ± ± ±. 89 Cl /L kg - h ± ± ± ± ± ± V /L kg ± ± ± ± ± ±. 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 ± ± Lag time /h ± ± 0. 8 t /2 ka /h ± ± t /2 ke /h. 22 ± ± t max /h ± ± 0. 7 c max /mg L ± ± AUC 0 t /mg L - h ± ± Cl /L kg - h ± ± V /L kg ± ± See Tab. 2 for the lengend. 珋 x ± s n = 6. 3 AUC AUC 0 7 RP- HPLC Zhang JF Zhang DF. Study advancement in pharmalcological actions of total saponins of Panax notoginseseng J. Med Recapit 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 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

5 Hasegawa H Sung JH Matsumiya S Uchiyama M. Main ginseng saponin metabolites formed by intestinal bacteria J. Planta Med Yu ZG. Establish and validate biopharmarceutical analysis method M Li HZ. Biopharmarceutical Analysis. Beijing China Medical Science Press Han M. Studies on oral absorption of Panax notoginsenoside and preparation of W /O microemulsion for oral administration D. Shanghai Fudan University 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 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 China 2. Guangxi Traditional Chinese Medical University Nanning China 3. Guangxi Wuzhou Pharmaceutical Group Co. Ltd. Wuzhou China Abstract OBJECTIVE To investigate pharmacokinetics of Panax notoginseng saponins in Beagle dogs. METHODS enteric-coated capsules 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 ± vs 0. 6 ± h for R ± vs. 74 ± h for Rg ± vs ± 0. 7 h for Rb Lag times were prolonged ± 0. 6 vs ± 0. h for R ± vs ± 0. 0 h for Rg ± 0. 2 vs ± h for Rb. The relative bioavailability of R Rg Rb and was % 07. 9% % and 55. 3% respectively. After integration the main pharmacokinetic parameters of capsules and enteric-coated capsules respectively were AUC 0 t ± vs ± mg L - h Lag times ± 0. 8 vs ± 0. 3 h t max ± 0. 7 vs ± 0. 3 h Cl ± vs. 84 ± 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 and Natural Science Foundation of Guangxi Zhuang Autonomuous Region 200GXNSFB03068 Corresponding author LIU Hua-gang hgliu@ 263. net Tel