Dose proportionality and comparison of single and multiple dose pharmacokinetics of fexofenadine (MDL 16455) and its enantiomers in healthy male volunteers

The pharmacokinetics and dose proportionality of fexofenadine, a new non-sedating antihistamine, and its enantiomers were characterized after single and multiple-dose administration of its hydrochloride salt. A total of 24 healthy male volunteers (31 +/- 8 years) received oral doses of 20, 60, 120 and 240 mg fexofenadine HCl in a randomized, complete four-period cross-over design. Subjects received a single oral dose on day 1, and multiple oral doses every 12 h on day 3 through the morning on day 7. Treatments were separated by a 14-day washout period. Serial blood and urine samples were collected for up to 48 h following the first and last doses of fexofenadine HCl. Fexofenadine and its R(+) and S(-) enantiomers were analysed in plasma and urine by validated HPLC methods. Fexofenadine pharmacokinetics were linear across the 20-120 mg dose range, but a small disproportionate increase in area under the plasma concentration-time curve (AUC) (< 25%) was observed following the 240 mg dose. Single-dose pharmacokinetics of fexofenadine were predictive of steady-state pharmacokinetics. Urinary elimination of fexofenadine played a minor role (10%) in the disposition of this drug. A 63:37 steady-state ratio of R(+) and S(-) fexofenadine was observed in plasma. This ratio was essentially constant across time and dose. R(+) and S(-) fexofenadine were eliminated into urine in equal rates and quantities. All doses of fexofenadine HCl were well tolerated after single and multiple-dose administration.     

Regulation of hepatic 7 alpha-hydroxylase expression and response to dietary cholesterol in the rat and hamster

Although dietary cholesterol raises plasma total and low density lipoprotein (LDL) cholesterol concentrations, the response to a given intake of cholesterol varies enormously among different species and even among individuals of the same species. The mechanisms responsible for differing sensitivity to dietary cholesterol were examined by comparing the rat, which is able to adapt to large fluctuations in sterol intake or loss with little change in plasma LDL levels, with the hamster, where changes in sterol balance strongly influence plasma LDL concentrations. When fed the same cholesterol-free diet, hepatic 7 alpha-hydroxylase activity was 16-fold higher in the rat than in the hamster. As a consequence, rates of hepatic cholesterol synthesis were 20-fold higher in the rat than in the hamster. In both species, hepatic cholesterol synthesis was suppressed > 90% in response to increasing loads of dietary cholesterol. However, the quantitative importance of this adaptive mechanism was much greater in the rat since the absolute reduction in hepatic cholesterol synthesis in the rat (2,110 nmol/h/g) was much larger than in the hamster (103 nmol/h/g). In the rat, the high basal level of 7 alpha-hydroxylase expression was further induced by substrate (cholesterol) allowing these animals to convert excess dietary cholesterol to bile acids efficiently. In contrast, the low basal level of enzyme expression in the hamster was not induced by dietary cholesterol. Thus, the low basal rates of bile acid and cholesterol synthesis coupled with a lack of 7 alpha-hydroxylase induction by cholesterol render the hamster much more sensitive than the rat to the cholesterolemic effects of dietary cholesterol.     

Favorable influence of ssDNA-functionalized SWCNT on the navigation pattern of C. elegans

Microsystem Technologies - Single-Walled Carbon Nanotubes (SWCNTs) are widely used as potential carriers in drug delivery systems. The objective of this work was to observe the effects of pristine,...     

CORRELATING CHEMICAL AND WATER PURITY TO THE SURFACE METAL ON SILICON WAFER DURING WET CLEANING PROCESS

Trace metals in hydrogen peroxide and high-purity water, used in wet cleaning of wafers, is correlated to the metallic contamination of the wafer surface since metal contamination adversely impacts IC device yield. Hydrogen peroxide with different level of trace metals, ranging from 100 ppt level to 10 ppb level, is used in the experiment to determine the level of selected metal deposition on the silicon surface. Significant amounts of these trace metallic impurities can be removed by subsequent treatment of the silicon wafer by an acidified solution of water. Contamination of a wafer surface by sodium is also correlated to the level of sodium present in deionized water used in the final rinsing of the wafer. The threshold and mechanism for metal deposition for various metals on wafer surfaces are different. This information is useful in determining purity requirements for process chemicals and improving the wet cleaning process for the next generation of semiconductor devices.     

Geomorphic diversity as a river management tool and its application to the Ganga River,India

Understanding of geomorphic processes and the determination of geomorphic diversity in catchments are prerequisites for the sustainable rehabilitation of river systems and for reach‐scale assessment of river health. The Ganga River system in India is a large, complex system consisting of several long tributaries, some >1,000 km, originating from 2 distinct hinterlands—the Himalaya to the north and the cratons to the south. Traversing through a diverse climatic regime across the Plain and through precipitation zones ranging from 600 mm/year near Delhi to 1,200 mm/year in the eastern plains, the Ganga River system has formed very diverse landform assemblages in 3 major geomorphic domains. We have recognized 10 different river classes for the trunk river from Gangotri (source) to Farakka (upstream of its confluence with the Brahmaputra) based on (a) landscape setting, (b) channel and active floodplain properties, and (c) channel planform parameters. The mountainous stretch is characterized by steep valleys and bedrock channels and is dominated by large‐scale sediment production and transport through hill slope processes. The alluvial part of the river is characterized by 8 different river classes of varying reach lengths (60–300 km) many of which show sharp transitions in landscape setting. We have highlighted the application of this approach for the assessment of habitat suitability, environmental flows, and flood risk all of which have been significantly modified during the last few decades due to large‐scale anthropogenic disturbances. We suggest that the diversity embedded in this geomorphic framework can be useful for developing a sustainable river management programme to “work with” the contemporary character and behaviour of rivers.     

Desulphurization of coals and chars by treatment in various atmospheres between 400 and 600 °C

Desulphurization of fifteen US coals of rank ranging from anthracite to sub-bituminous B and five high-temperature chars by carbon monoxide and other gases and gas mixtures between 400 and 600 °C has been studied. The sulphur content of the parent coals ranged between 3.0 and 7.3% and that of the chars between 1.3 and 3.8% by weight. A comparison between air, nitrogen, carbon monoxide, and steam-carbon monoxide mixtures as desulphurizing gases shows the order of desulphurizing ability as

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