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    Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty

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    Access Status
    Open access
    Authors
    Tan, S.J.
    Cockcroft, M.
    Page-Sharp, Madhu
    Arendts, G.
    Davis, T.M.E.
    Moore, Brioni
    Batty, Kevin
    Salman, S.
    Manning, L.
    Date
    2020
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Tan, S.J. and Cockcroft, M. and Page-Sharp, M. and Arendts, G. and Davis, T.M.E. and Moore, B.R. and Batty, K.T. et al. 2020. Population pharmacokinetic study of ceftriaxone in elderly patients, using cystatin C-based estimates of renal function to account for frailty. Antimicrobial Agents and Chemotherapy. 64 (10): ARTN e00874-20.
    Source Title
    Antimicrobial Agents and Chemotherapy
    DOI
    10.1128/AAC.00874-20
    ISSN
    0066-4804
    Faculty
    Faculty of Health Sciences
    School
    Curtin Medical School
    Funding and Sponsorship
    http://purl.org/au-research/grants/nhmrc/1047105
    http://purl.org/au-research/grants/nhmrc/1036951
    http://purl.org/au-research/grants/nhmrc/1124130
    Remarks

    Originally published in Antimicrobial Agents and Chemotherapy.

    URI
    http://hdl.handle.net/20.500.11937/88948
    Collection
    • Curtin Research Publications
    Abstract

    Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.5, 1, 4, 8, and 24 h after administration of 1 g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified using the Edmonton frailty scale and grip strength via a hand dynamometer. Estimates of glomerular filtration rate were determined using creatinine-based and cystatin C-based equations. Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance improved significantly with a cystatin C-based estimate of renal function that accounted for frailty. Simulations indicate that the combined effects of ranges of size and renal function resulted in a 6-fold range in peak ceftriaxone concentrations and 9-fold range in total exposure (area under the concentration-time curve [AUC]). For elderly patients with moderate or severe renal impairment, 48-h dosing results in greater trough concentrations and total exposure than the trough concentrations and total exposure in patients with normal renal function receiving 24-h dosing. Cystatin C-based measures of renal function improved predictions of ceftriaxone clearance in elderly patients.

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