+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

The metabolism of the 5HT3 antagonists ondansetron, alosetron and GR87442 I: a comparison of in vitro and in vivo metabolism and in vitro enzyme kinetics in rat, dog and human hepatocytes, microsomes and recombinant human enzymes



The metabolism of the 5HT3 antagonists ondansetron, alosetron and GR87442 I: a comparison of in vitro and in vivo metabolism and in vitro enzyme kinetics in rat, dog and human hepatocytes, microsomes and recombinant human enzymes



Xenobiotica; the Fate of Foreign Compounds in Biological Systems 37(8): 832-854



The metabolism of the structurally related 5HT3 antagonists ondansetron, alosetron and GR87442 in the rat, dog and human was determined in hepatocytes, liver microsomes and human recombinant microsomes. The profiles of phase I metabolites were similar in human hepatocytes and microsomes. The metabolites of all three compounds produced in rat, dog and human microsomes and hepatocytes were similar to those seen in vivo, with the major routes of metabolism being N-dealkylation and/or hydroxylation. There was more extensive metabolic processing in hepatocytes than in microsomes; however, sequential metabolism was less extensive in vitro compared with in vivo. The pharmacokinetics of the three 5HT3 antagonists investigated were dominated by CYP3A4 (and/or 2C9) compared with CYP1A2 in man, possibly determined by enzyme capacity rather than relative enzyme affinity. These data support the use of rat, dog and human hepatocytes for the prediction of in vivo metabolites of ondansetron, alosetron and GR87442.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 017425977

Download citation: RISBibTeXText

PMID: 17701832

DOI: 10.1080/00498250701485575


Related references

The metabolism of the 5HT3 antagonists, ondansetron, alosetron and GR87442 II: investigation into the in vitro methods used to predict the in vivo hepatic clearance of ondansetron, alosetron and GR87442 in the rat, dog and human. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 37(8): 855-869, 2007

Metabolism of chamaechromone in vitro with human liver microsomes and recombinant human drug-metabolizing enzymes. Planta Medica 80(6): 493-497, 2014

Metabolism of ebracteolata compound B studied in vitro with human liver microsomes, HepG2 cells, and recombinant human enzymes. Drug Metabolism and Disposition: the Biological Fate of Chemicals 38(12): 2157-2165, 2011

In vitro profiling of the metabolism and drug-drug interaction of tofogliflozin, a potent and highly specific sodium-glucose co-transporter 2 inhibitor, using human liver microsomes, human hepatocytes, and recombinant human CYP. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 45(3): 230-238, 2015

In vitro characterization of hepatic flavopiridol metabolism using human liver microsomes and recombinant UGT enzymes. Pharmaceutical Research (New York) 19(5): 588-594, 2002

In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomes. Drug Metabolism and Disposition: the Biological Fate of Chemicals 29(12): 1638-1643, 2001

In vitro metabolism of a new oxazolidinedione hypoglycemic agent utilizing liver microsomes and recombinant human cytochrome P450 enzymes. Journal of Pharmaceutical and Biomedical Analysis 37(2): 351-358, 2005

Identification of cytochrome P450s involved in the metabolism of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1) using human recombinant enzymes and rat liver microsomes in vitro. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 47(8): 667-672, 2016

In vitro glucuronidation kinetics of deoxynivalenol by human and animal microsomes and recombinant human UGT enzymes. Archives of Toxicology 89(6): 949-960, 2016

In Vitro Metabolism of BIIB21, an Inhibitor of Heat Shock Protein 9, in Liver Microsomes and Hepatocytes of Rats, Dogs, and Humans and Recombinant Human Cytochrome P45 Isoforms. Drug Metabolism and Disposition 40(4): 680-693, 2012

Study of in vitro metabolism of m-nisoldipine in human liver microsomes and recombinant cytochrome P450 enzymes by liquid chromatography-mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis 97: 65-71, 2015

In vitro metabolism of BIIB021, an inhibitor of heat shock protein 90, in liver microsomes and hepatocytes of rats, dogs, and humans and recombinant human cytochrome P450 isoforms. Drug Metabolism and Disposition: the Biological Fate of Chemicals 40(4): 680-693, 2012

Studies comparing in vivo:in vitro metabolism of three pharmaceutical compounds in rat, dog, monkey, and human using cryopreserved hepatocytes, microsomes, and collagen gel immobilized hepatocyte cultures. Drug Metabolism and Disposition: the Biological Fate of Chemicals 29(7): 1042-1050, 2001

In vitro metabolism of magnolin and characterization of cytochrome P450 enzymes responsible for its metabolism in human liver microsomes. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 41(5): 358-371, 2011

In vitro metabolism of a new cardioprotective agent, KR-33028 in the human liver microsomes and cryopreserved human hepatocytes. Archives of Pharmacal Research 28(11): 1287-1292, 2005