Selective effects of nitric oxide on the disposition of chlorzoxazone and dextromethorphan in isolated perfused rat livers

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Ragini Vuppugalla, Reza Mehvar

Abstract

The rapid and direct effects of nitric oxide (NO) donors sodium nitroprusside (SNP) and isosorbide dinitrate (ISDN) on the hepatic and biliary disposition of chlorzoxazone (CZX), a marker of CYP2E1, and dextromethorphan (DEM), a marker of CYP2D1, were studied in a single-pass isolated perfused rat liver model. Livers (n = 30) were perfused with constant concentrations of NO donors (0-120 min) in addition to infusion of CZX or DEM (60-120 min), and periodical outlet and bile samples were collected. Both ISDN and SNP significantly reduced (30 and 60%, respectively) the hepatic extraction ratio of CZX and decreased (50 and 70%, respectively) the recovery of the CYP2E1-mediated metabolite, 6-hydroxychlorzoxazone, in the outlet perfusate and bile. As for DEM, both NO donors increased (up to 3.5-fold) the recovery of the CYP2D1-mediated metabolite dextrorphan (DOR) in the outlet perfusate. However, this was associated with a simultaneous decrease (50-75%) in the excretion of the metabolite into the bile, thus resulting in no change in the overall recovery of DOR as a result of NO donor treatment. The decrease in the biliary excretion of DOR was caused by NO-induced simultaneous reductions in both the conjugation of DOR and biliary cl...Continue Reading

References

Jan 1, 1990·Clinical and Experimental Pharmacology & Physiology·W T Abed
Nov 1, 1990·Chemical Research in Toxicology·R PeterC S Yang
Dec 1, 1986·Infection and Immunity·P GhezziC A Dinarello
Aug 7, 1981·Journal of Chromatography·D M BaaskeJ E Carter
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·O G KhatsenkoJ R Vane
Jan 1, 1993·Archives of Biochemistry and Biophysics·D A WinkR W Nims
Aug 1, 1996·Journal of Pharmaceutical and Biomedical Analysis·A J KillardD P Bogan
Apr 1, 1997·Biopharmaceutics & Drug Disposition·M H CourtD J Greenblatt
Jan 9, 1998·Drug Metabolism Reviews·E T Morgan
Aug 28, 1998·Naunyn-Schmiedeberg's Archives of Pharmacology·M Feelisch
Jun 20, 2002·Pharmacology & Toxicology·Yoshiaki KawashimaToshiyuki Someya
Jan 4, 2003·Archives of Pharmacal Research·Im-Sook SongChang-Koo Shim
Mar 30, 1960·Annals of the New York Academy of Sciences·A H CONNEY, J J BURNS
Mar 25, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·David S RiddickJohn Y L Chiang
Sep 24, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ragini Vuppugalla, Reza Mehvar
Mar 22, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ragini Vuppugalla, Reza Mehvar

❮ Previous
Next ❯

Citations

Apr 26, 2012·Chemical Research in Toxicology·Slobodan Rendic, F Peter Guengerich
Jan 25, 2013·World Journal of Gastroenterology : WJG·Seok Ling OngAshley R Dennison
Dec 25, 2009·The Journal of Surgical Research·Gianpiero GravanteAshley R Dennison
Jun 12, 2009·The Journal of Surgical Research·Gianpiero GravanteAshley R Dennison
Feb 13, 2010·Journal of Proteome Research·Yang ZhangYouhe Gao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antianginal Drugs: Mechanisms of Action

Antianginal drugs, including nitrates, beta-blockers, and calcium channel blockers, are used in the treatment of angina pectoris. Here is the latest research on their use and their mechanism of action.