PMID: 21970858Oct 6, 2011Paper

Quantitative prediction of intestinal glucuronidation of drugs in rats using in vitro metabolic clearance data

Drug Metabolism and Pharmacokinetics
Takako FurukawaToshio Teramura

Abstract

UDP-glucuronosyltransferase (UGT) is highly expressed in the small intestine and catalyzes the glucuronidation of small molecules, which may affect the oral bioavailability of drugs. However, no method of predicting the in vivo observed fraction of absorbed drug (F(a)F(g)) affected by UGT has yet been established. Here, we investigated the relationship between F(a)F(g) and in vitro clearance of nine UGT substrates (ketoprofen, tolcapone, telmisartan, raloxifene, entacapone, resveratrol, buprenorphine, quercetin, and ezetimibe) via UGT in intestinal microsomes (CL(int, UGT)) in rats. F(a)F(g) was calculated from pharmacokinetic parameters after intravenous and oral administration or using the portal-systemic concentration difference method, with values ranging from 0.027 (ezetimibe) to 1 (tolcapone). Glucuronides of model compounds were observed in the portal plasma after oral administration, with CL(int, UGT) values ranging from 57.8 (tolcapone) to 19,200 µL/min/mg (resveratrol). An inverse correlation between F(a)F(g) and CL(int, UGT) was observed for most compounds and was described using a simplified intestinal availability model reported previously. This model gave accurate predictions of F(a)F(g) values for three in-house ...Continue Reading

References

Nov 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·T D LindstromG W Whitaker
Mar 1, 1981·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·D BrewsterM A McLeavy
Nov 1, 1981·Journal of Pharmacobio-dynamics·K YamaokaT Uno
Jul 1, 1993·Pharmaceutical Research·B Davies, T Morris
Jun 29, 2000·Biochemical and Biophysical Research Communications·G KuhnleU Hahn
May 23, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Daniel C KempJeffrey C Stevens
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Jean-Francois MarierMurray P Ducharme
Jan 14, 2003·Pharmaceutical Research·Chongwoo YuRichard B van Breemen
Feb 14, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·M K ShelbyC D Klaassen
Apr 16, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Smarajit Maiti, Guangping Chen
Aug 12, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Andrew WilliamsSimon E Ball
Mar 17, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Eun Ju JeongMing Hu
Mar 22, 2005·Molecular Nutrition & Food Research·Elisabeth Wenzel, Veronika Somoza
May 6, 2005·Clinical Pharmacokinetics·Teddy KosoglouKevin B Alton
Jun 11, 2005·Pharmaceutical Research·Xiao ChenMoses S S Chow
Oct 20, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·David B Buckley, Curtis D Klaassen
Feb 3, 2007·Expert Opinion on Drug Metabolism & Toxicology·Joseph K Ritter
Nov 6, 2007·Molecular Pharmaceutics·Li ZhangGe Lin
Apr 8, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C HuangG Chen
May 12, 2009·Drug Metabolism and Pharmacokinetics·Masuhiro NishimuraShinsaku Naito
Apr 1, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Keitaro KadonoToshio Teramura

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Citations

Aug 31, 2013·Cancer Chemotherapy and Pharmacology·Zheng SunJia Liu
Oct 1, 2015·Nuclear Medicine and Biology·Hiroki HashimotoMing-Rong Zhang
Aug 22, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Takako FurukawaToshio Teramura
Dec 18, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Keitaro KadonoToshio Teramura
May 1, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Takako FurukawaToshio Teramura
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Yoichi NaritomiKenji Tabata
Nov 23, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Amol A RajeKasim A Mookhtiar
Nov 6, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Takaya KutsukakeMiki Nakajima
Jun 12, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Fumihiro NakamoriToshio Teramura
Aug 30, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yoshiki MatsudaShinji Yamashita
Aug 6, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Rui LiHugh A Barton

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