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  • 1990-1994
  • 1975-1979  (2)
  • 1978  (2)
  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of currently available anti-arthritic gold preparations to inhibit lysosomal glycosidases from rheumatoid synovial fluid and normal human serum was studied in vitro. It was shown that these preparations differ markedly in their ability to inhibit the enzymes. Gold thioglucose (Solganal) did not inhibit β-glucuronidase (β-GLUC), β-N-acetylglucosaminidase (β-NAG) or hyaluronidase (HASE). Chloro(triethylphosphine)gold (SK&F 36914) was a potent inhibitor of β-NAG only. Sodium aurothiomalate (Myochrysine and sodium 3-aurothio-2-propanol-1-sulphonate (Allyochrisine) were inhibitors of all three enzymes, notably β-GLUC. Kinetic analysis of inhibition by aurothiomalate demonstrated apparent competitive inhibition with β-GLUC, but non-competitive inhibition with HASE and β-NAG β-GLUC was also strongly inhibited by silver and copper thiomalates. The concentrations of these drugs required for effective inhibition of lysosomal glycosidases probably exceed those attained in serum and therefore preclude this action extracellularly. It is suggested that durg sequestration and retention within phagocytic cells facilitates inhibition of glycosaminoglycan catabolism that mediates cleavage of glucuronidic linkages of hyaluronic acid and chondroitin sulphates. The hypothesis that gold dompounds act in vivo by attenuating the activity of lysosomal enzymes is discussed in relation to these and previous findings.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: p-Chlorophenoxyisobutyric acid ; clofibrate ; steady-state plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of clofibrinic acid have been estimated under conditions approaching the steady-state during a ten-day period of administration as clofibrate or as a calcium clofibrinate-carbonate combination (1:1 w/w) at a dosage interval of 12 h. Formulation — related differences in bioavailability were not significant, and the 95% confidence limits of these differences were within −2% to +8% of the mean for the reference formulation of clofibrate. The mean steadystate plasma concentrations of clofibrinic acid measured on the tenth day of dosing were 116 µg/ml±22 S.D. and 119 µg/ml±23 S.D. after administration of 885 mg as clofibrate and the calcium clofibrinate-carbonate combination respectively. The peaks of mean plasma concentrations were 70 µg/ml±15 S.D., 119 µg/ml±32 S.D. and 131 µg/ml±26 S.D. on the first, fifth and tenth day of dosing with clofibrate, and 62 µg/ml±13 S.D., 127 µg/ml±S.D. and 143 µg/ml±25 S.D. on the corresponding days of dosing with the calcium clofibrinate-carbonate combination. After the last dose on the tenth day of dosing, the mean apparent half-lives of elimination of clofibrinic acid from plasma were 24.2 h±4.4 S.D. and 25.5 h±3.2 S.D. after administration of clofibrate and the calcium clofibrinate-carbonate combination respectively.
    Type of Medium: Electronic Resource
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