Biliary excretion of glycyrrhetinic acid: glucuronide-conjugate determination following a pharmacokinetic study of rat bile.
Liquorice is a commonly prescribed herb in traditional Chinese medicine with the primary constituent, glycyrrhetinic acid (GA) responsible for the toxic effects arising from its chronic consumption. Hepatic transformation and biliary excretion of GA are significant and well-documented pharmacokinetic pathways in humans, while glucuronide conjugates are the major identified metabolites. Here we report the role of bile in GA bioconversion in rats; this being achieved following intravenous administration of GA to Sprague-Dawley rats at a dose of 2 mg/kg with bile fluid analyzed for 3 h post-injection using HPLC. The maximum concentration of glucuronides was detected about 30 min post-administration, while the cumulative biliary excretion of glucuronides after 3 h was found to be 63.6 ± 6.4%. Our findings indicate a relatively high rate of biliary excretion for GA via the formation of glucuronide conjugates, and as a result of these findings, glucuronidation can be firmly regarded as a primary detoxification pathway for GA in rats.
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, Jiangsu, China; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, the University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Yang
Y
Lu
Jing
J
Jing
Weichao
W
Ren
Jing
J
Zhu
Zhixia
Z
Qiu
Ning
N
Li
Xiaonan
X
Li
Di
D
Zhao
Harendra S
HS
Parekh
Xijing
X
Chen
D000818:Animals; D001646:Bile / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D020719:Glucuronides / Q000737:chemistry*; D006034:Glycyrrhetinic Acid / Q000493:pharmacokinetics*; D065669:Hepatobiliary Elimination; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D020719:Glucuronides; D006034:Glycyrrhetinic Acid
biliary excretion; glucuronide metabolite; glycyrrhetinic acid