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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1985), S. 689-691 
    ISSN: 1432-1041
    Keywords: indomethacin ; Osmosin ; plasma and synovial fluid ; polyarthritis ; inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary ‘Osmosin’ (sodium indomethacin trihydrate, now withdrawn) produced a constant rate of release of indomethacin into the gut. Paired plasma and synovial fluid samples were obtained at regular intervals following a single dose of ‘Osmosin’ (19 patients) and after continuous daily dosing (15 patients). Indomethacin is rapidly absorbed and plasma concentrations maintained in the range 0.3 to 0.6 µg/ml after the first 4 h. Equilibrium between plasma and synovial fluid occurs, with SF/plasma ratios 0.74 to 0.82 12–24 h after a single dose and up to 0.96 thereafter. The indomethacin synovial fluid/plasma profile is changed by Osmosin from the pattern of a short half-life drug to the pattern typical of a long half-life drug. Results from serial samples obtained by use of indwelling cannulae (in vein and knee joint) show close agreement with our single paired sampling technique. Our method may have theoretical disadvantages but it has many practical advantages.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: diclofenac sodium ; synovial fluid levels ; hydroxylated metabolites ; rheumatoid patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and synovial fluid concentrations of diclofenac sodium and its principal hydroxylated metabolites have been measured in sixteen rheumatoid patients on chronic therapy to investigate possible reasons for the drug's extended duration of action despite its apparent short elimination half-life in plasma. Diclofenac was detected in synovial fluid 2 h after dosing but at a lower level than in plasma. Thereafter synovial fluid concentrations remained relatively constant through to 11 h post-dosing whereas plasma levels in the same period declined rapidly from an initially high peak to near the sensitivity limit of the assay. Hydroxylated metabolites (free + conjugated) were rapidly formed with measurable concentrations of the 4′ and 5 mono and dihydroxy derivatives being detected in plasma 2 h after dosing; levels of the 3′ hydroxy metabolite were negligible at this time. Initially plasma levels of all metabolites were higher than those in synovial fluid but after 4 h synovial fluid levels were equal to or slightly higher than those in plasma. The significance of these findings is discussed in relation to the drug's overall clinical effect.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 331-334 
    ISSN: 1432-1041
    Keywords: diclofenac sodium ; rheumatoid disease ; healthy subjects ; serum albumin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic data for diclofenac sodium has been well established in healthy volunteers, whereas in patients with rheumatoid arthritis very little information is available in the literature. A single oral dose of enteric-coated diclofenac sodium was given to 10 patients with active rheumatoid disease, adopting the same procedures used for a group of 10 healthy volunteers in whom pharmacokinetic data was already available. Plasma specimens were collected over a period of 8h following administration and concentrations of diclofenac determined by GLC. Resulting plasma concentration curves were similar to those obtained in the healthy subjects in that areas under curves and terminal half-lives were comparable. However, peak concentrations of diclofenac were significantly reduced in the rheumatoid patients. The lower peak concentrations were correlated with the lower serum albumin levels in the patients which are associated with active rheumatoid disease.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: diclofenac sodium ; slow-release formulation ; plasma and synovial fluid concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and knee joint synovial fluid (SF) concentration of diclofenac sodium and its hydroxylated metabolites were measured after chronic dosing with the 100 mg polymer matrix formulation. Peak concentrations were reached in plasma and SF roughly after administration. Plasma concentrations then fell rapidly, but concentrations in SF were maintained for up to 25 h. The active metabolite was present in both fluids throughout the study period. The slow-release form showed a longer plasma/SF equilibration time than the conventional tablet had in a previous study. Prostaglandin E1 and F2a concentrations were lower in the early post-dose period but did not correlate with drug concentrations.
    Type of Medium: Electronic Resource
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