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Abstract A uricosuric agent, bucolome, has been shown to intensify the anticoagulant effect of warfarin. The aims of the present study were to clarify its mechanism(s) and to apply in vitro approaches for predicting this potentially life-threatening in vivo interaction. An in vivo study revealed...
Abstract Troglitazone (TRO) is an insulin sensitizer used in the treatment of type II diabetes. TRO is known to increase the activity of cytochrome P-450 (CYP) 3A in vivo. We have investigated the effect of TRO on CYP3A protein content and the activity of CYP3A (as measured by the formation of...
Abstract The pharmacokinetics of celecoxib, a cyclooxygenase-2 inhibitor, was characterized in beagle dogs. Celecoxib is extensively metabolized by dogs to a hydroxymethyl metabolite with subsequent oxidization to the carboxylic acid analog. There are at least two populations of dogs,...
Abstract The involvement of flavin-containing monooxygenases (FMOs) in the formation of xanomeline N- oxide was examined in various human and rat tissues. Expressed FMOs formed xanomeline N- oxide at a significantly greater rate than did expressed cytochromes P-450. Consistent with the...
Abstract Mass balance and metabolism of formoterol were investigated in six healthy men in an open study. Mean age was 49.7 years (range: 40–63). Simultaneous oral (mean dose 88.6 nmol, 49.3 MBq) and i.v. (mean dose 38.2 nmol, 21.4 MBq) doses of tritium-labeled formoterol were administered. The...
Abstract Cytochrome P-450 (CYP) 2J4 is a member of the recently identified CYP2J subfamily–part of the CYP superfamily–and is primarily expressed in rat small intestinal epithelium (enterocytes). Studies to determine small intestinal CYP2J4 inducibility by prototypic CYP inducers have been...
Abstract The urinary metabolites of 3-methyl-4-trifluoromethylaniline in the rat were characterized and quantified using a combination of 19 F NMR, HPLC-NMR ( 1 H and 19 F), and HPLC-mass spectrometry techniques. The major routes of metabolism were amine N -acetylation and methyl group C...
Abstract A study was conducted to investigate qualitative and quantitative aspects of the phase I metabolism of 3-methylindole (3MI) by porcine liver microsomes. Microsomal suspensions were prepared from the liver of 30 intact (uncastrated) male pigs. Metabolites produced in microsomal...
Abstract Telmisartan 1- O -acylglucuronide, the principal metabolite of telmisartan in humans, was characterized in terms of chemical stability and the structure of its isomerization products was elucidated. In addition, pharmacokinetics of telmisartan 1- O -acylglucuronide were assessed in rats...
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