Biliary Excretion of Glycyrrhetinic Acid: Glucuronide-Conjugate Determination Following a Pharmacokinetic Study of Rat Bile

2014 ◽  
Vol 28 (12) ◽  
pp. 1887-1889 ◽  
Author(s):  
Yang Lu ◽  
Jing Jing ◽  
Weichao Ren ◽  
Jing Zhu ◽  
Zhixia Qiu ◽  
...  
2021 ◽  
Author(s):  
Huan Gao ◽  
Qin Guo ◽  
Lishi Zhang ◽  
Jiannan Song ◽  
Dong Bai ◽  
...  

Abstract Background: Guizhi Decoction (GZD), a traditional Chinese medical formula, has been commonly used to treat fever, sweating, and cold in China. Methods: The high performance liquid chromatography -tandem mass spectrometry ( HPLC-MS/MS ) method was established for the determination of 10 compounds, including cinnamic acid , paeoniflorin, albiflorin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, and 6-gingerol. And the specificity, linearity, lower limit of quantification (LLOQ), lower limit of detection (LLOD), precision and accuracy, recovery, matrix effect, and stability were used to verify the HPLC-MS/MS method. This validated method was successfully applied for pharmacokinetic study of the 10 compounds in rat plasma after oral administration of GZD in three doses (40 g crude drug·kg −1 , 20 g crude drug·kg −1 , 10 g crude drug·kg −1 ) and intravenous injection of GZD extraction at a dose of 2.0 g crude drug·kg −1 .The measurements of pharmacokinetic parameters including AUC 0–∞ , T 1/2 , T max , C max , Vz_F, Cl_F, and MRT, were performed using a non-compartmental model with Winnonlin 8.1 software. Results: The results showed that 10 compounds were detected in plasma after oral administration of GZD. the compounds (except for glycyrrhetinic acid) reached the maximum blood concentration quickly, whose Tmax was about 0.1-0.2 min. And a total of 9 compounds were detected after intravenous injection of GZD. The plasma concentration-time curve of these compounds declines rapidly at the beginning, and then decreased slowly, indicating that the plasma concentration-time curves were double exponential function curves. Conclusions: In this study, the developed method was suitable for pharmacokinetic analysis of the main compounds of GZD in rat plasma, and may reveal the pharmacodynamic material basis of GZD and provide a reference for the rational use of GZD in the clinic.


1967 ◽  
Vol 105 (3) ◽  
pp. 1269-1274 ◽  
Author(s):  
M M Abou-el-Makarem ◽  
P Millburn ◽  
R L Smith ◽  
R T Williams

1. The extent of the excretion in the bile of the rat of benzene and 21 of its simple derivatives was studied. 2. Some 16 compounds of molecular weight less than 200, and including neutral molecules (benzene and toluene), aromatic acids, aromatic amines and phenols, were injected in solution intraperitoneally into biliary-cannulated rats. Metabolites in the bile were identified and estimated. The extent of biliary excretion of these compounds was low, i.e. 0–10% of the dose in 24hr., and most appeared in the bile mainly as conjugates. 3. The biliary excretion of six conjugates of molecular weight less than 300, including three glycine conjugates, one sulphate conjugate, one glucuronic acid conjugate and two acetyl derivatives, was low (less than 3% of the dose). 4. It is concluded that simple benzene derivatives of molecular weight less than about 300 are poorly excreted in rat bile.


2001 ◽  
Vol 914 (1-2) ◽  
pp. 77-82 ◽  
Author(s):  
Y.L. Chang ◽  
M.H. Chou ◽  
M.F. Lin ◽  
C.F. Chen ◽  
T.H. Tsai

2001 ◽  
Vol 281 (2) ◽  
pp. G515-G525 ◽  
Author(s):  
Im-Sook Song ◽  
Suk-Jae Chung ◽  
Chang-Koo Shim

The objective of this study was to examine whether ion pair complexation with endogenous bile salts in hepatocytes contributes to the preferential biliary excretion of organic cations (OCs). Tributylmethylammonium (TBuMA; mol wt 200) and triethylmethylammonium (TEMA; mol wt 116) were selected as model OCs that exhibit significant and negligible biliary excretion, respectively, in rats. The apparent lipophilicity of TBuMA, but not that of TEMA, was increased by the presence of either rat bile or specific bile salts, suggesting the formation of lipophilic ion pair complexes for TBuMA with bile salts in the liver. The uptake of TBuMA into canalicular liver plasma membrane (cLPM) vesicles, but not that of TEMA, was increased in the presence of bile salts, with a significant increase for both ATP-dependent transport and passive diffusion. The uptake of TBuMA in the presence of the bile salts was inhibited by representative P-glycoprotein (P-gp) substrates and vice versa, suggesting the involvement of P-gp in the canalicular excretion of TBuMA-bile salt complexes in vivo. Increased affinity toward P-gp is suggested as the mechanism responsible for the increased ATP-dependent transport for the ion pair complexes. We propose that ion pair formation with bile slats in hepatocytes may be responsible for the preferential biliary excretion of high-molecular-weight OCs including TBuMA.


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