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  • 1
    Electronic Resource
    Electronic Resource
    Influence of chronic diflunisal treatment on the plasma levels, metabolism and excretion of indomethacin (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 7-15 
    Details
    ISSN: 1432-1041
    Keywords: indomethacin ; diflunisal ; pharmacokinetics ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The single-dose pharmacokinetics of indomethacin following 100 mg rectally was measured in two groups of 8 healthy subjects before and after diflunisal 500 mg p.o. once daily, or 500 mg in the morning and 1000 mg in the evening, until steady state conditions were reached. A further group of 8 healthy subjects was given 50 mg indomethacin rectally before and after diflunisal 500 mg p.o. twice daily. High dose diflunisal (1500 mg/day) decreased the renal clearance of indomethacin from 21.9 to 1.8 ml/min (92%) and reduced the renal excretion of both unchanged (63%) and conjugated (82%) indomethacin. The apparent total body clearance (0.12 l/h/kg), apparent volume of distribution (0.98 l/kg), and volume of distribution at steady state (0.80 l/kg) were decreased by 47%, 35% and 30%. The maximum plasma concentration (2.4 µg/ml) and total area under the curve (13.0 µg × h/ml) were increased by 40% and 119%, respectively. The terminal elimination half-life (5.7 h) and mean residence time (6.7 h) were slightly prolonged (7.0 h and 8.8 h) in the presence of diflunisal. The contribution of metabolism to the overall elimination of indomethacin was increased by only 2%. Similar results were obtained when the subjects were challenged with the low dose of diflunisal (500 mg/day), although the magnitude of the changes were smaller. The interaction between indomethacin and diflunisal may be due to competition both at the metabolic (conjugation) and the excretory (tubular secretion) levels. When the subjects were given 50 mg indomethacin and diflunisal 1000 mg/day simultaneously, the achieved maximum plasma concentration of indomethacin (2.53 µg/ml) was comparable to that seen after 100 mg in the absence of diflunisal (3.1 µg/ml), but the AUC was greater (21.7 µg × h/ml vs 13.0 µg × h/ml). Adverse central nervous reactions were more frequent and more pronounced at higher plasma indomethacin concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609416
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  • 2
    Electronic Resource
    Electronic Resource
    High-pressure liquid chromatographic determination of acetylsalicylic acid, salicylic acid, diflunisal, indomethacin, indoprofen and indobufen (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 375-378 
    Details
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; diflunisal ; indomethacin ; salicylic acid ; indoprofen ; indobufen ; high-pressure liquid chromatography ; plasma level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A high-pressure liquid chromatographic technique was developed which allowed concurrent measurement of acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma. ASA was extensively deacetylated to SA not only in vivo but also in vitro, even in frozen plasma. The in vitro conversion could be prevented by physostigmine. In vivo, ASA was eliminated within few hours, whereas SA was continuously present following daily administration of conventional doses of ASA. A slight modification of a similar method, originally developed for naproxen determination [9], was found appropriate for measurement of the SA derivative diflunisal, of two non-SA antiinflammatory agents, indomethacin and indoprofen, and of a related anti-platelet agent, indobufen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00615408
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