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OBJECTIVE Shenmai injection(SMI) is a kind of herbal injection widely used in China derived from SHENMAI formula.SMI is the alcohol extraction part of Panax ginseng and Ophiopogon japonicas.It’s generally accepted that ginsenosides are the major components in SMI according to their abundance and activity.METHODS In order to monitor the kinetic profile of major components in SMI during long-term treatment and to further analyze its connection to toxic effect,a 6-month toxicokinetic experiment was performed in 24 beagle dogs.Dogs were equally and randomly divided into four groups: control group(0.9% NaCl solution per day;n = 6),low-dosage Group(2 g·kg-1 per day;n = 6),medium-dosage Group(6 g·kg-1 per day;n = 6) and High-dosage Group(20 g·kg-1 per day;n = 6).Vehicle and SMI were i.v.drip injected everyday for 180 continuous days(6 months).Blood sample were collected at 0,90,180 d after the beginning of the administration of SMI.The concentration of ginsenoside Rb1,Rb2,Rc,Rd,Re,Rf and Rg1 in plasma were determined simultaneously for the first time by liquid chromatography-tandem mass spectrometry(LC-MS /MS) and liquid-liquid extraction method.Non-compartmental parameters were further simultaneously calculated and analyzed.Meanwhile,the level of bodyweight,AST,ALT and CK were also monitored to evaluate the toxic effect caused by SMI.RESULTS According to the results,significant differences existed between 20(S)-protopanaxadiol type(PPD type) and 20(S)-protopanaxatriol type(PPT type) ginsenosides.Only accumulation of ginsenoside PPD type ginsenosides can be observed with the proceeding of the experiment.Although long-term administration of 6 g /mL and 20 g.ml-1 SMI caused a slowing down in the growth of bodyweights,no toxic effect could be reviewed from the level of ALT,AST and CK.CONCLUSION Although no significant toxic effect could be observed during the toxicokinetic study,the kinetic profile of PPD type ginsenoside was severely altered.Since SMI is wild used in the co-administration with other drugs,the changing of the metabolism of PPD type ginsenosides may led to a higher risk of drug-drug interaction.The exposure of PPD type ginsenosides should be carefully monitored during the long-term administration of SMI,especially when SMI is co-administra-ted with other drugs.
OBJECTIVE Shenmai injection (SMI) is a kind of herbal injection widely used in China derived from SHENMAI formula. MI is the alcohol extraction part of Panax ginseng and Ophiopogon japonicas. It’s generally accepted that ginsenosides are the major components in SMI according to their abundance and activity. METHODS In order to monitor the kinetic profile of major components in SMI during long-term treatment and to analyze it again to toxic effect, a 6-month toxicokinetic experiment was performed in 24 beagle dogs. four groups: control group (0.9% NaCl solution per day; n = 6), low-dosage Group (2 g · kg -1 per day; n = 6) ; n = 6) and High-dosage Group (20 g · kg-1 per day; n = 6) .Vehicle and SMI were ivdrip injected everyday for 180 continuous days (6 months). Blood samples were collected at 0,90,180 d after the beginning of the administration of SMI. The concentration of ginsenoside Rb1, Rb2, Rc, Rd, Re, Rf and R g1 in plasma were determined for the first time by liquid chromatography-tandem mass spectrometry (LC-MS / MS) and liquid-liquid extraction method. Non-compartmental parameters were also successively calculated and analyzed. Meanwhile, the level of bodyweight, AST , ALT and CK were also monitored to evaluate the toxic effect caused by SMI.RESULTS According to the results, significant difference existed between 20 (S) -protopanaxadiol type (PPD type) and 20 (S) -protopanaxatriol type (PPT type) ginsenosides .Only accumulation of ginsenoside PPD type ginsenosides can be observed with the proceeding of the experiment. Although long-term administration of 6 g / mL and 20 g.ml-1 SMI caused a slowing down in the growth of bodyweights, no toxic effect could was reviewed from the level of ALT, AST and CK.CONCLUSION Although no significant toxic effect could be observed during the toxicokinetic study, the kinetic profile of PPD type ginsenoside was severely altered altered. Since SMI is wild used in the co-administration with other drugs, the changing of the metabolism of PPD type ginsenosides may led to a higher risk of drug-drug interaction. The exposure of PPD type ginsenosides should be carefully monitored during the long-term administration of SMI, especially when SMI is co -administra-ted with other drugs.