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The role of the polymorphic cytochrome p450 2D6 (CYP2D6) in the pharmacokinetics of atomoxetine hydrochloride [(-)-N-methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride; LY139603] has been documented following both single and multiple doses of the drug. In this study, the influence of the CYP2D6 polymorphism on the overall disposition and(More)
These studies were designed to characterize the disposition and metabolism of atomoxetine hydrochloride [(-)-N-methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride; formerly know as tomoxetine hydrochloride] in Fischer 344 rats and beagle dogs. Atomoxetine was well absorbed from the gastrointestinal tract and cleared primarily by metabolism with(More)
2-Acetoxy-5-(alpha-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (prasugrel) is a novel thienopyridine prodrug with demonstrated inhibition of platelet aggregation and activation. The biotransformation of prasugrel to its active metabolite, 2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic(More)
The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6-12(More)
Inhibition of Na+/K+-ATPase and Mg2+-ATPase activities by in vitro exposure to Cd2+, Pb2+ and Mn2+ was investigated in rat brain synaptic plasma membranes (SPMs). Cd2+ and Pb2+ produced a larger maximal inhibition of Na+/K+-ATPase than of Mg2+-ATPase activity. Metal concentrations causing 50% inhibition of Na+/K+-ATPase activity (IC50 values) were Cd2+ (0.6(More)
Diarylsulfonylureas, such as N-(4-chlorophenyl)aminocarbonyl-2,3-dihydro-1-indene-5-sulfonamide (LY186641, Sulofenur) and N-(4-chlorophenyl)aminocarbonyl-4-methylbenzene sulfonamide (LY181984), have been shown to be effective antitumor agents in a variety of in vivo and in vitro animal models. Their mechanism of action is unknown but does not appear to be(More)
Cephalosporin antibiotics, such as cephaloridine (Cld), are known to be nephrotoxic in vivo and in vitro. In vivo, Cld causes proximal tubule necrosis in rabbits which is preceded by glutathione (GSH) depletion and, under certain conditions, inhibition of mitochondrial function. In vitro, Cld causes GSH depletion, lipid peroxidation, and inhibition of rat(More)
A sensitive and selective liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the determination of atomoxetine and its metabolites (4-hydroxyatomoxetine, N-des-methylatomoxetine, and 4-hydroxyatomoxetine-O-glucuronide) has been developed for human plasma and urine. Using stable-labeled internal standards, the method proved to be accurate(More)
Cephaloridine (Cld) is a nephrotoxic cephalosporin antibiotic. The intracellular biochemical changes that occur leading to Cld-induced nephrotoxicity may involve lipid peroxidation and/or mitochondrial injury. The purpose of this report was to examine and correlate the biochemical changes induced by Cld in vivo and in vitro with the observed pathological(More)
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