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  • Immunotoxicity  (1)
  • metabolism  (1)
  • 1
    ISSN: 1432-1041
    Keywords: amodiaquine ; Plasmodium falciparum malaria ; monodesethylamodiaquine ; HPLC ; pharmacokinetics ; prophylaxis ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of monodesethylamodiaquine was studied in four healthy subjects after a single oral dose of 10 mg/kg amodiaquine base. Amodiaquine was not found in any sample, but the major metabolite monodesethylamodiaquine was detected and was assumed to be the sole derivative that contributed significantly to antimalarial activity in the blood. The best fit for the decay of the metabolite was obtained with a three-compartment model. The half-lives of the first two phases were 3.2 to 11.4 h for t1/2α1 and 22.7 to 50.3 h for t1/2α2 in plasma. The half-life of the terminal phase ( t1/2β) was between 9 and 18.2 days. The concentration in whole blood was 4- to 6-times higher than in plasma. Three schedules (alternate days, weekly, daily) of the conventional prophylactic dose of 10 mg/kg per week were compared in six other healthy subjects. There were significant differences in the plasma monodesethylamodiaquine levels between the three schedules.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Comparative clinical pathology 3 (1993), S. 63-66 
    ISSN: 1433-2981
    Keywords: Immunotoxicity ; Risk assessment ; Preclinical testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunotoxic effects include direct immunotoxicity, hypersensitivity and autoimmunity. Each effect requires a specific strategy to identify and assess the risks involved. At the moment, 2- or 3-tier protocols are considered the best modalities to detect an unexpectedly immunosuppressive compound and presumably an immunoenhancing compound as well. Such protocols are best conducted as 21–90 day rat studies. Contact sensitisation and anaphylaxis models in guinea pigs or mice are also useful tools to predict hypersensitivity. Finally, only a few systemic autoimmune reactions may be predicted in mice or rats using the popliteal lymph node assay. Thanks to improved standardisation and interlaboratory validation, an increased risk for infections and lymphomas (immunosuppression), contact dermatitis, anaphylaxis (macromolecular compounds only) and systemic autoimmune reactions (e.g. lupus) can reasonably be predicted. As few guidelines are available concerning the immunotoxicity assessment of novel chemicals, it is proposed that tier-1 and contact sensitisation should be performed routinely whatever the compound whereas additional testing may be required on a case-by-case approach, taking into account the modalities of exposure (e.g. dose and duration), the exposed population and the nature of the compound (e.g. pharmaceuticals).
    Type of Medium: Electronic Resource
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