Objective: To investigate the urinary soy isoflavone metabolites from women, female piglets and rats fed with diet containing soy protein. Methods: Urinary samples from human and animals were collected after soy diet ...Objective: To investigate the urinary soy isoflavone metabolites from women, female piglets and rats fed with diet containing soy protein. Methods: Urinary samples from human and animals were collected after soy diet consumption. Identification for soy isoflavone metabolites in urine samples was processed using an Agilent Bruker LC Esquire ion trap system. Quantification of aglycone and conjugated soy isoflavone metabolites were also analyzed using a method published previously. Results: Identification studies showed that aglycones and conjugates of soy isoflavone metabolites were found in women and porcine samples. Interestingly, glucuronide conjugate of equol, besides glucuronide conjugates of genistein and daidzein, were found in rat urine. Glucuronide conjugate of equol was the major metabolite found in rat urine. A quantitative study showed that conjugated forms of isoflavones were more than 90% in woman urine, were between 80.5% and 84.5% in female porcine urine, and were less than 50% in female rat urine. Conclusion: Equol is the major metabolite found in female rat urine, but it is not found in woman or female porcine urine. Urinary profiles show that porcine model is more appropriate for mimicking human soy diet consuming studies.展开更多
A new andrographolide metabolite 1 was isolated from human urine samples after oral administration. The structure was determined to be 3-carbonylandrographolide-19-O-β-D-glu- curonide on the basis of chemical evidenc...A new andrographolide metabolite 1 was isolated from human urine samples after oral administration. The structure was determined to be 3-carbonylandrographolide-19-O-β-D-glu- curonide on the basis of chemical evidences and spectral analysis, especially by 2D-NMR techni- ques.展开更多
Thienorphine(TNP)is a new partial opioid agonist currently developed as a promising drug candidate with the intended clinical indication for the treatment of opioid dependence.The pharmacokinetic profile and biliary e...Thienorphine(TNP)is a new partial opioid agonist currently developed as a promising drug candidate with the intended clinical indication for the treatment of opioid dependence.The pharmacokinetic profile and biliary excretion of TNP and its glucuronide conjugate(TNP-Glu)were investigated after oral administration of TNP in rats.The concentrations of TNP and TNP-Glu were simultaneously quantified using a LC-MS/MS method.A double peak phenomenon was observed in TNP plasma concentration–time curves with the secondary peak appeared at 6–8 h.A slower decline of plasma concentrations in the terminal phase was observed for TNP with T1/2 of 7.01 h.TNP-Glu was the predominant component in rat plasma and bile.Its plasma level was about 10 times higher than TNP and the 24 h accumulative bile excretion rate was 23%.Enterohepatic circulation of TNP and TNP-Glu was evaluated using a paired rat model.In bile-donor rats,no double-peak was detected and the elimination half life of TNP was significantly shortened(3.71 h)when compared to intact rats(7.01 h,P<0.05).Both TNP and TNP-Glu were detected in bile-recipient rats.Their exposures in recipient rats due to enterohepatic circulation were 15.6%and 42.6%for the parent drug and the metabolite,respectively.The deconjugation of the glucuronide conjugate and the reabsorption of free TNP were further confirmed in in situ perfused rat intestinal preparations.These results indicate that the enterohepatic circulation has a significant influence on the systemic exposure of the parent drug and its glucuronide conjugate,particularly on the terminal elimination of TNP,which may result in the prolonged retention of the drug in body.展开更多
文摘Objective: To investigate the urinary soy isoflavone metabolites from women, female piglets and rats fed with diet containing soy protein. Methods: Urinary samples from human and animals were collected after soy diet consumption. Identification for soy isoflavone metabolites in urine samples was processed using an Agilent Bruker LC Esquire ion trap system. Quantification of aglycone and conjugated soy isoflavone metabolites were also analyzed using a method published previously. Results: Identification studies showed that aglycones and conjugates of soy isoflavone metabolites were found in women and porcine samples. Interestingly, glucuronide conjugate of equol, besides glucuronide conjugates of genistein and daidzein, were found in rat urine. Glucuronide conjugate of equol was the major metabolite found in rat urine. A quantitative study showed that conjugated forms of isoflavones were more than 90% in woman urine, were between 80.5% and 84.5% in female porcine urine, and were less than 50% in female rat urine. Conclusion: Equol is the major metabolite found in female rat urine, but it is not found in woman or female porcine urine. Urinary profiles show that porcine model is more appropriate for mimicking human soy diet consuming studies.
文摘A new andrographolide metabolite 1 was isolated from human urine samples after oral administration. The structure was determined to be 3-carbonylandrographolide-19-O-β-D-glu- curonide on the basis of chemical evidences and spectral analysis, especially by 2D-NMR techni- ques.
基金supported by Chinese National S&T Major Special Project on Major New Drug Innovation(Grant numbers:2009ZX09301-002 and 2011ZX09101-005-01).
文摘Thienorphine(TNP)is a new partial opioid agonist currently developed as a promising drug candidate with the intended clinical indication for the treatment of opioid dependence.The pharmacokinetic profile and biliary excretion of TNP and its glucuronide conjugate(TNP-Glu)were investigated after oral administration of TNP in rats.The concentrations of TNP and TNP-Glu were simultaneously quantified using a LC-MS/MS method.A double peak phenomenon was observed in TNP plasma concentration–time curves with the secondary peak appeared at 6–8 h.A slower decline of plasma concentrations in the terminal phase was observed for TNP with T1/2 of 7.01 h.TNP-Glu was the predominant component in rat plasma and bile.Its plasma level was about 10 times higher than TNP and the 24 h accumulative bile excretion rate was 23%.Enterohepatic circulation of TNP and TNP-Glu was evaluated using a paired rat model.In bile-donor rats,no double-peak was detected and the elimination half life of TNP was significantly shortened(3.71 h)when compared to intact rats(7.01 h,P<0.05).Both TNP and TNP-Glu were detected in bile-recipient rats.Their exposures in recipient rats due to enterohepatic circulation were 15.6%and 42.6%for the parent drug and the metabolite,respectively.The deconjugation of the glucuronide conjugate and the reabsorption of free TNP were further confirmed in in situ perfused rat intestinal preparations.These results indicate that the enterohepatic circulation has a significant influence on the systemic exposure of the parent drug and its glucuronide conjugate,particularly on the terminal elimination of TNP,which may result in the prolonged retention of the drug in body.
