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  • Pharmacokinetic modeling to determine the minimum effective dose of disease-specific antibodies for preventing hepatitis A post-exposure

    Author(s)
    Young, Megan K
    Ng, Shu-Kay
    Nimmo, Graeme R
    Cripps, Allan W
    Griffith University Author(s)
    Young, Megan K.
    Cripps, Allan W.
    Nimmo, Graeme R.
    Ng, Shu Kay Angus
    Year published
    2020
    Metadata
    Show full item record
    Abstract
    Background: The minimum effective dose of intramuscular polyvalent immune globulin for prevention of hepatitis A post-exposure is unknown. In Australia current dosing is according to weight category. Methods: The peak concentration and decay of hepatitis A antibodies after intramuscular dosing of immune globulin in adults was modeled utilizing published parameters. Models simulated dosing according to current Australian guidelines, then adjusted the dose in clinically relevant increments to estimate the optimal dose of hepatitis A antibodies for post-exposure prophylaxis of nonimmune individuals. Optimal dosing assumed a ...
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    Background: The minimum effective dose of intramuscular polyvalent immune globulin for prevention of hepatitis A post-exposure is unknown. In Australia current dosing is according to weight category. Methods: The peak concentration and decay of hepatitis A antibodies after intramuscular dosing of immune globulin in adults was modeled utilizing published parameters. Models simulated dosing according to current Australian guidelines, then adjusted the dose in clinically relevant increments to estimate the optimal dose of hepatitis A antibodies for post-exposure prophylaxis of nonimmune individuals. Optimal dosing assumed a target serum concentration of hepatitis A antibodies of the correlate of protection plus a 10% margin of error at an incubation period. The effect of weight on hepatitis A antibody concentration at an incubation period under current guidelines was examined by fixing weight in 5 kg increments. Results: Current dosing guidelines in Australia may underdose people who weigh in excess of 85 kg. The optimal dose of hepatitis A-specific antibodies according to the model was 3.6, 2.5, and 1.9 IU/kg assuming 50%, 75% and 100% bioavailability respectively. Conclusions: For individuals in Australia recommended passive immunization as post-exposure prophylaxis and weighing in excess of 85 kg, conservative management would include dosing between 2.5 and 3.6 IU hepatitis A antibodies/kg.
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    Journal Title
    Expert Opinion on Drug Metabolism & Toxicology
    Volume
    16
    Issue
    7
    DOI
    https://doi.org/10.1080/17425255.2020.1763303
    Subject
    Pharmacology and Pharmaceutical Sciences
    Science & Technology
    Life Sciences & Biomedicine
    Biochemistry & Molecular Biology
    Pharmacology & Pharmacy
    Toxicology
    Publication URI
    http://hdl.handle.net/10072/397392
    Collection
    • Journal articles

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