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Valerian preparations alone or in combination with hops are popular over-the-counter products used for sleep disturbances or anxiety. Therefore, it is important to characterize the effect of these products on the activity of human drug-metabolizing enzymes. The inhibitory effects of valerian and...
UDP-glucuronosyltranferases (UGTs) affect the disposition of drugs and other xenobiotics by catalysing the conjugation of glucuronic acid to available oxygen, nitrogen, and sulfur atoms. Several related mammalian isoforms of UGT are expressed that have different binding affinities and turnover...
The metabolism of fluvoxamine to fluvoxamino acid is known to involve a two-step oxidation process via an alcohol intermediate, fluvoxamino alcohol. The present study was carried out to identify the cytochrome P450 (CYP) enzyme(s) involved in the metabolism of fluvoxamine to fluvoxamino alcohol...
Imidafenacin (IM), 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide, is a newly synthesized antimuscarinic drug developed for the treatment of overactive bladder. To predict clinically relevant drug interactions in the metabolism of IM, the paper investigated: (1) the major enzymes...
The in vitro metabolism of (−)-fenchone was examined in human liver microsomes and recombinant enzymes. The biotransformation of (−)-fenchone was investigated by gas chromatography-mass spectrometry. (−)-Fenchone was found to be oxidized to 6- exo -hydroxyfenchone, 6- endo -hydroxyfenchone...
This study was undertaken to examine the inductive effects of two triazole antifungal agents, myclobutanil and triadimefon, on the expression of hepatic cytochrome P450 (CYP) genes and on the activities of CYP enzymes in male Sprague–Dawley rats. Rats were dosed with the conazoles at three dose...
The characterization of brimonidine metabolites presents some challenges since brimonidine and its metabolites generate few structurally informative fragment ions in the LC-MS/MS spectra. The objective of the current study is to use on-line hydrogen/deuterium (H/D) exchange LC-MS/MS and...
Recent studies have demonstrated that the pregnane X receptor (PXR) is a key regulator of cytochromes P450 3A (e.g. CYP3A4 in human) gene expression. As a result, activation of PXR may lead to CYP3A4 protein over-expression. Because induction of CYP3A4 could result in clinically important...
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