Distribution studies

Initially, it was beheved that the abiUty of xanthines phosphodiesterase (PDF) led to bronchodilation (Fig. 2). One significant flaw in this proposal is that the concentration of theophylline needed to significantly inhibit PDE in vitro is higher than the therapeutically useful semm values (72). It is possible that concentration of theophylline in airways smooth muscle occurs, but there is no support for this idea from tissue distribution studies. Furthermore, other potent PDE inhibitors such as dipyridamole [58-32-2] are not bronchodilators (73). EinaHy, although clinical studies have shown that neither po nor continuous iv theophylline has a direct effect on circulating cycHc AMP levels (74,75), one study has shown that iv theophylline significant potentiates the increase in cycHc AMP levels induced by isoproterenol (74). 

Plasma levels of 3—5 p.g/mL are obtained two hours after adraiinistration of 200 mg ketoconazole. No accumulation in the bloodstream was noted after a 30-wk treatment with this dose. The half-life is approximately eight hours. When ketoconazole is taken with meals, higher plasma levels are obtained. Distribution studies using radioactive ketoconazole in rats show radioactivity mainly in the Hver and the connective tissue. Radioactivity is also present in the subcutaneous tissue and the sebaceous glands. After one dose of 200 mg in humans, ketoconazole is found in urine, saUva, sebum, and cenimen. Like miconazole, the mode of action is based on inhibition of the cytochrome P-450 dependent biosynthesis of ergosterol. This results in disturbed membrane permeabiUty and membrane-bound enzymes (8,10,23,25). 

The characteristic function and the moment generating function are important tools for computing moments of distributions, studying limits of sequences of distributions, and finding the distribution of sums of independent variables. If Z — X + F, where X and T are independently distributed according to the distribution functions F(x) and 6( y) respectively, the distribution function of Z is given by... 

Lapidus (LI) described liquid residence-time distribution studies for air-water and air-hydrocarbon in cocurrent, downward flow through a column of 2-in. diameter and 3-ft height. Spherical glass beads of 3.5. mm diameter and cobalt molybdate catalyst cylinders of -in. diameter were used as packing materials. 

S3B Pharmacokinetics Guidance for Repeated Dose Tissue Distribution Studies Toxicity Testing... 

Based on the distributions studied so far, the simulation results show that at low TEA/Tl ratios the site distribution is probably unlmodal or bimodal with predominantly HAFD sites (l.e., > 90 %) undergoing first order decay. Beyond the critical value of TEA/Ti (10,8) a different distribution must exist for 6 to be > 1-0... 

Bergman K. 1983a. Application and results of the whole-body autoradiography in distribution studies of organic solvents. CRC Crit Rev Toxicol 12 59-118. 

MIXFLOl and MIXFL02 - Mixed-Flow Residence Time Distribution Studies... 

Support for the limited metabolism of IMPA to MPA with resultant retention of the MPA is provided by distribution studies of Sarin (GB). Twenty-four hours after intravenous injection of [3H]-labeled Sarin, unextractable label was present in all tissues except the plasma and kidney. At least some unextractable label was presumed by the study authors to be protein-bound MPA (Little et al. 1986, 1988). The concentration of bound MPA was found to be 20-65% of bound IMPA in different mouse brain areas, with the highest concentration found in the hypothalamus. 

In animals, radiolabel distribution studies demonstrate rapid movement of the label to the liver. Average plasma concentrations of label were greater than average blood concentrations in mice, rats, and dogs after oral administration of a single dose of 225 mg/kg diisopropyl methylphosphonate (Hart 1976). 

Mazzucchelli, C Pannacci, M., Nonno, R. et al. (1996). The melatonin receptor in the human brain cloning experiments and distribution studies. Brain Res. Mol. 

You have been asked to carry out a residence time distribution study on a reactor network that has evolved over the years by adding whatever size and type of reactor was available at the moment. The feed stream presently contains 1... 

Distribution studies by whole-body autoradiography in rats and monkeys revealed accumulation of radiolabel in the liver, kidney, lung, adrenal cortex and stomach. In fetuses exposed in utero, only the eye lens accumulated radiolabel at a higher concentration than that observed in maternal blood (Sandberg and Slanina 1980). 

Thus, D-fructose can be synthesized by a reversal of the Embden-Meyer-hof glycolytic pathway (see Fig. 2) in animals and in many other organisms. Unless evidence is available to the contrary, it is generally assumed that this pathway is present in any organism, since distribution studies indicate the system is ubiquitous. However, a different pathway is used by Pseudomonas saccharophila, which utilizes one mole of D-glucose or D-gluconic acid... 

Yamamoto, K., Y. Yamamoto, and C. Kuwahara. 1979. A blood cyanide distribution study in the rabbits intoxicated by oral route and by inhalation. Zeit. Rechtsmedizin 83 313-317. 

There were no effects at any of the doses tested on the histopathology of the brain for any duration or route of exposure (Gorzinski et al. 1985 NTP 1977, 1989 Weeks et al. 1979). This observation is consistent with tissue distribution studies which indicate that hexachloroethane has no particular affinity for the brain tissues (Fowler 1969b). 

Continuous Multicomponent Distillation Column 501 Gas Separation by Membrane Permeation 475 Transport of Heavy Metals in Water and Sediment 565 Residence Time Distribution Studies 381 Nitrification in a Fluidised Bed Reactor 547 Conversion of Nitrobenzene to Aniline 329 Non-Ideal Stirred-Tank Reactor 374 Oscillating Tank Reactor Behaviour 290 Oxidation Reaction in an Aerated Tank 250 Classic Streeter-Phelps Oxygen Sag Curves 569 Auto-Refrigerated Reactor 295 Batch Reactor of Luyben 253 Reversible Reaction with Temperature Effects 305 Reversible Reaction with Variable Heat Capacities 299 Reaction with Integrated Extraction of Inhibitory Product 280... 

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