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Abstract N -Hydroxy- N ′-(4- n -butyl-2-methylphenyl)formamidine (HET0016) is a potent inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) formation by specific cytochrome P450 isoforms. Previous studies have demonstrated that administration of HET0016 inhibits brain formation of 20-HETE and...
Abstract The prodrug (2 R ,4 S )-4-(3-chlorophenyl)-2-(3,5-dimethyl-4-(4′-hydroxy-3′-isopropylbenzyl)phenoxy)methyl-2-oxido-1,3,2-dioxaphosphonane (MB07811) of a novel phosphonate-containing thyroid hormone receptor agonist...
Abstract Overdoses of γ-hydroxybutyrate (GHB), a drug of abuse, result in coma, respiratory arrest, and death. The objective of this study was to evaluate a potential GHB detoxification strategy by inhibiting the monocarboxylate transporter (MCT)-mediated renal reabsorption of GHB in rats, using...
Abstract The pharmacokinetics, metabolism, and excretion of torcetrapib, a selective inhibitor of human cholesteryl ester transfer protein, were investigated in healthy human male volunteers after oral administration of 14 Ctorcetrapib (120-mg dose). The total mean recovery of radiolabeled dose...
Abstract Several cytochrome P450 (P450) enzymes have been identified in the heart, and their levels have been reported to be altered during cardiac hypertrophy. Moreover, there is a strong correlation between P450-mediated arachidonic acid metabolites and the pathogenesis of cardiac hypertrophy....
Abstract Silymarin, an extract from seeds of Silybum marianum , is used by 8 to 33% of patients to self-treat chronic viral hepatitis C in the United States. Studies in humans and rodents suggest that biliary excretion of glucuronide and sulfate conjugates is the major route for silymarin's...
Abstract The effect of oxaliplatin against colorectal cancer is superior to that of cisplatin, but the molecular mechanism(s) involved is not clear. We found previously that oxaliplatin, but not cisplatin, was transported by human (h) and rat organic cation transporter 3 (OCT3)/ SLC22A3 . In the...
Abstract The entactogen, 3,4-methylenedioxy-methamphetamine (MDMA), is a chiral drug that is mainly metabolized by N -demethylation and demethylenation. The involvement of cytochrome P450 (P450) isozymes in these metabolic steps has been studied by inhibition assays with human liver microsomes...
Abstract Cytochrome P4503A4 (CYP3A4) is the most abundant cytochrome P450 in adult human liver and small intestine and oxidizes numerous clinically, physiologically, and toxicologically important compounds. The metabolic activity of CYP3A4 in patients varies at least 10-fold in vivo, and CYP3A4...
Abstract Liquiritigenin 2,3-dihydro-7-hydroxy-2-(4-hydroxyphenyl)-( S )-4 H -1-benzopyran-4-one is one of the major active compounds of MF101, an herbal extract currently in clinical trials for the treatment of hot flashes and night sweats in postmenopausal women. MF101 is a selective estrogen...
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