Pharmacokinetics and metabolism of jatrorrhizine, a gastric prokinetic drug candidate

Biopharmaceutics & Drug Disposition
Rong ShiNengneng Cheng

Abstract

Jatrorrhizine, a protoberberine alkaloid derived from Coptis chinensis, is currently under investigation as a natural gastric prokinetic drug candidate. In vitro and in vivo studies were conducted to characterize its pharmacokinetics and metabolism. After intravenous administration, the plasma concentration kinetics and major metabolites in rats were investigated. The metabolic kinetics, key cytochrome P450 enzymes and UDP-glucuronosyltransferase isoforms (UGTs) of jatrorrhizine were studied in rat liver microsomes (RLMs). After intravenous administration, plasma jatrorrhizine concentrations showed a biphasic decline, dose-independent clearance and half-life of terminal elimination phase, and a relatively large distribution volume. The metabolic pathway for the conversion of jatrorrhizine was important for its elimination. In addition, the demethylated and glucuronidated products were found to be the major metabolites in rats. The enzyme kinetics for both demethylation and glucuronidation were fitted to the hyperbolic Michaelis-Menten equation in RLMs. CYP3A1/2 and CYP2D2 were mainly responsible for demethylation, and UGT 1A1 and 1A3 were responsible for glucuronidation in RLMs. The metabolic properties of jatrorrhizine suggest...Continue Reading

References

Mar 1, 1995·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S J BaldwinR J Chenery
Jun 1, 1994·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S E ClarkeR J Chenery
Jun 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kaoru KobayashiKan Chiba
Dec 1, 2004·Therapeutic Drug Monitoring·Nicolas PicardPierre Marquet
Mar 25, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Annalise Di MarcoRalph Laufer
Aug 22, 2006·Current Drug Metabolism·Li-Zi ZhaoShufeng Zhou
Aug 23, 2006·Acta Pharmacologica Sinica·Yi-tong LiuGuang-ji Wang
Jul 25, 2008·Biomedical Chromatography : BMC·Yi ZhangYong Chen
Jul 11, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Natália Valadares de MoraesVera Lucia Lanchote
Oct 28, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Emilija MakajiDenis J Crankshaw
Apr 9, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Silvio AprileGiorgio Grosa
Sep 15, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xia ZhangSu Zeng
May 21, 2011·European Journal of Pharmacology·JianYe YuanDaZheng Wu

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Citations

Jan 3, 2013·Journal of Pharmaceutical Sciences·Zhaodan TanNengneng Cheng
Jan 10, 2013·Biopharmaceutics & Drug Disposition·Hui ZhouNengneng Cheng
Jun 5, 2014·Journal of Food Science·Ping ChenNengneng Cheng
Jan 30, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Songcan LiuJian Jiang
Mar 16, 2017·Drug Metabolism Reviews·Kun WangFeng Qiu
May 30, 2015·Artificial Cells, Nanomedicine, and Biotechnology·Timothy N Estep
Apr 7, 2021·The Journal of Pharmacy and Pharmacology·Janiqua RolleRaphael N Alolga

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