Interaction Between Clopidogrel and Panax Notoginseng Saponins

2020 ◽  
Author(s):  
Yunzhen Hu ◽  
Xi Yang
Keyword(s):  
Metabolic Rate ◽  
Rat Liver ◽  
Active Metabolite ◽  
Liver Microsomes ◽  
Panax Notoginseng ◽  
Combination Group ◽  
Specific Substrate ◽  
Rat Liver Microsomes ◽  
Panax Notoginseng Saponins ◽  
Sandwich Method

Abstract Background: Panax notoginseng saponins (PNS) is commonly used in combination with clopidogrel in clinic. This study was to investigate the effect of PNS on the pharmacokinetics of clopidogrel active metabolite CAMD and the effect on the activities of clopidogrel metabolic enzymes in rats. Methods: In pharmacokinetics studies, the rats were divided into clopidogrel and combination groups, and continuously administered for seven days. The concentration of CAMD was determined by LC-MS/MS. In enzymes studies, the rats were divided into control and PNS groups. After administration for seven days, CYP2C19 and CYP3A4 activities were measured by the metabolic rate of the specific substrate in rat liver microsomes. The activity of CES1 enzyme was determined by double antibody sandwich method.Results: PNS significantly increased AUC0-∞ of CAMD from 43.1±11.6 to 72.0±25.1 h·ng/mL (p<0.05). Combination group had lower CL/F and Vd/F than clopidogrel group (p<0.05). PNS significantly decreased the activity of CYP3A4 and CES1 (p<0.01), but no significant effect on CYP2C19.Conclusions: The combination use of PNS and clopidogrel produced a significant increase in the AUC of clopidogrel active metabolite CAMD. PNS could inhibit the activity of CYP3A4 and CES1 enzyme in rat.

Simple method for determination of the active metabolite of the inotropic drug pimobendan in rat liver microsomes

2000 ◽  
Vol 744 (1) ◽  
pp. 189-193 ◽  
Author(s):  
Shin-ichiro Kuriya ◽  
Shigeru Ohmori ◽  
Mayuko Hino ◽  
Chiaki Senda ◽  
Kenji Sakai ◽  
...  
Keyword(s):  
Rat Liver ◽  
Active Metabolite ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Simple Method ◽  
Inotropic Drug

Metabolic Analysis of Triptolide Microspheres in Human, Dog, Rabbit and Rat Liver Microsomes with UPLC-MS/MS Method

2020 ◽  
Vol 17 ◽  
Author(s):  
LiJuan Wang ◽  
Yan Liu ◽  
Rui Li ◽  
DongXian He
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Liver Microsomes ◽  
Good Precision ◽  
Kinetics Parameters ◽  
Measure Concentration ◽  
Standard Curve ◽  
Variation Of Parameters

Objectives: Triptolide (TPL) has been shown to have a good clinical effect on rheumatoid arthritis (RA). We designed TPL microspheres (TPL-MS) and investigated its metabolic behavior in human, dog, rabbit and rat liver microsomes (HLM, DLM, RLM and SDRLM) with UPLC-MS/MS method. Methods: First, a UPLC-MS/MS method was established to measure concentration of TPL in samples. The sample was separated on a C18 column (2.1×100 mm, 1.8μm) and eluted with a gradient elution. The precursor ion/product ion were m/z 378.1/361.0 for TPL and 260.0/116.2 for the internal standard. Then T1/2, Vmax and CLint were calculated from the above data. Finally, the metabolites of TPL-MS were identified by high-resolution UPLC-MS/MS. The sample was separated on a C18 column (2.1×100 mm, 2.2 μm) and eluted with isocratic elution. Mass spectrometric detection was carried out on a thermo Q-exactive mass spectrometer with HESI. The scanning range of precursor ions was from m/z 50 to m/z 750. Result and Discussion: Through several indicators including standard curve, precision, accuracy, stability, matrix effect and recovery rate, the enzymatic kinetics parameters including T1/2, Vmax and CLint were completed. Several metabolites of TPL-MS were identified. Conclusion: UPLC-MS/MS method is an accurate and sensitive method for determination of TPL in liver microsome samples with good precision, accuracy and stability. The variation of parameters indicated that the microspheres can delay the elimination of TPL in liver microsomes. The metabolism of TPL-MS varied among species, but no new metabolites appeared.

scholarly journals The metabolism of gelsevirine in human, pig, goat and rat liver microsomes

2021 ◽  
Author(s):  
Hua‐Hai Zhang ◽  
Wen‐Jia Yang ◽  
Ya‐Jun Huang ◽  
Wen‐Jing Li ◽  
Shuo‐Xin Zhang ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes

scholarly journals Detoxification of the tricyclic antidepressant opipramol and its analog – IS-noh by UGT enzymes before and after activation by phase I enzymes in rat liver microsomes

2021 ◽  
Author(s):  
Anna Mieszkowska ◽  
Koleta Hemine ◽  
Anna Skwierawska ◽  
Ewa Augustin ◽  
Zofia Mazerska
Keyword(s):  
Phase I ◽  
Rat Liver ◽  
Phase Ii ◽  
Oxidation Product ◽  
Liver Microsomes ◽  
Correct Selection ◽  
Rat Liver Microsomes ◽  
Recombinant Enzymes ◽  
Data Set ◽  
Phase I Enzymes

AbstractThe present studies were carried out to evaluate the simultaneous one-pot metabolism of opipramol (IS-opi) and analog (IS-noh) by phase I and phase II enzymes present in rat liver microsomes (RLM) as an alternative to separate testing with recombinant enzymes. This approach allows for more time-saving and cost-effective screening of the metabolism of newly discovered drugs. We also considered that the lack of results for phase II, including UGT, often creates problems in correct selection of valuable compounds. Moreover, microsomes data set is richer in the contest and provides medical scientist to determine also the susceptibility of drugs to undergo phase I and then phase II. In the present work, we have shown that IS-noh was metabolized in vitro by phase I enzymes to the oxidation product, which was next transformed with UGTs to glucuronide. The results showed also that the previously known oxidation product of opipramol was changed to previously no reported glucuronidation product by UDP-glucuronosyltransferases. In addition, unlike IS-noh, opipramol did not prove to be the substrate for UGTs. Therefore, tricyclic antidepressants depending on the structure can trigger a different response after contact with UGT enzymes. Some will metabolize directly with UGTs, others only after activation by phase I enzymes.

scholarly journals Oxidation of docosahexaenoic acid by rat liver microsomes.

1984 ◽  
Vol 259 (9) ◽  
pp. 5776-5783 ◽  
Author(s):  
M VanRollins ◽  
R C Baker ◽  
H W Sprecher ◽  
R C Murphy
Keyword(s):  
Docosahexaenoic Acid ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes
Sign in / Sign up

Export Citation Format

Share Document