ABSTRACT:These studies were designed to characterize the disposition and metabolism of atomoxetine hydrochloride [(؊)-N-methyl-␥-(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 the majority of its metabolites being excreted into the urine, 66% of the total dose in the rat and 48% in the dog. Fecal excretion, 32% of the total dose in the rat and 42% in the dog, appears to be due to biliary elimination and not due to unabsorbed dose. Nearly the entire dose was excreted within 24 h in both species. In the rat, low oral bioavailability was observed (F ‫؍‬ 4%) compared with the high oral bioavailability in dog (F ‫؍‬ 74%). These differences appear to be almost purely mediated by the efficient first-pass hepatic clearance of atomoxetine in rat. The biotransformation of atomoxetine was similar in the rat and dog, undergoing aromatic ring hydroxylation, benzylic oxidation (rat only), and Ndemethylation. The primary oxidative metabolite of atomoxetine was 4-hydroxyatomoxetine, which was subsequently conjugated forming O-glucuronide and O-sulfate (dog only) metabolites. Although subtle differences were observed in the excretion and biotransformation of atomoxetine in rats and dogs, the primary difference observed between these species was the extent of first-pass metabolism and the degree of systemic exposure to atomoxetine and its metabolites.

No abstract

No abstract

Heating experiments in EBT-S have been conducted in steady-state plasmas at continuous wave power levels up to 20 kW in the ion cyclotron range of frequencies (15–30 MHz). Power coupling efficiencies and wave propagation measurements have been obtained at reduced power levels over the frequency range 15–50 MHz. Wave dispersion properties are in qualitative agreement with simplified theory. Substantial ion heating is obtained in deuterium plasmas above 25 MHz, the point at which wave propagation begins. At this frequency, only the 3rd-10th ion cyclotron harmonics of deuterium are present in the core plasma. Ion heating under these circumstances is considerably greater than theoretically predicted for EBT-S parameters. A residual proton component is also heated. However, collisional energy transfer from the protons to the deuterons is too small to account for the deuteron heating. The stored energy of the relativistic electron annuli increases substantially with the application of wave power. Near the antenna, the stored energy more than doubles at a power level of 15 kW. The mechanism producing this dramatic effect is not well understood at present. A small reduction in the ambipolar electric field is also observed during wave heating.

No abstract