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pubmed-article:3125532pubmed:abstractTextConjugation of racemic E-10-hydroxynortriptyline (E-10-OH-NT) with glucuronic acid was studied in the liver microsomal fraction of rats and humans. The diastereomeric glucuronides of E-10-OH-NT were resolved and quantitated by HPLC. Only the (+)-enantiomer was glucuronidated in liver microsomes from humans. Rat liver microsomes catalyzed the formation of both glucuronides. Phenobarbital pretreatment of rats increased the glucuronidation of both enantiomers about five-fold. The formation rate of (+)-E-10-OH-NT glucuronide varied from 5.5 to 33.2 pmol/mg x min, in microsomes from 13 humans. High activity was found in individuals previously treated with pentobarbital. Inhibition experiments with human liver microsomes showed that amitriptyline is a potent competitive inhibitor of (+)-E-10-OH-NT glucuronidation. p-Nitrophenol, paracetamol and 2-hydroxydesipramine also inhibited this reaction.lld:pubmed
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pubmed-article:3125532pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:3125532pubmed:articleTitleGlucuronidation of the enantiomers of E-10-hydroxynortriptyline in human and rat liver microsomes.lld:pubmed
pubmed-article:3125532pubmed:affiliationDepartment of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.lld:pubmed
pubmed-article:3125532pubmed:publicationTypeJournal Articlelld:pubmed
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pubmed-article:3125532pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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