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Desacetylcefotaxime

Clinical Implications of an Active Metabolite in Infants and Children

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Summary

At present, desacetylcefotaxime represents the only major metabolite from a third generation cephalosporin that attains and maintains effective antimicrobial plasma and tissue concentrations following therapeutic administration of its parent drug (i.e. cefotaxime). Therapeutic concentrations of desacetylcefotaxime are produced in neonates, infants, children and adults, although because of normal developmental changes in renal function, the plasma clearance of the drug is reduced in neonates and young infants. Previous investigations of the pharmacokinetics of desacetylcefotaxime have not only demonstrated effective penetration into various tissues and fluids, but also that alterations in plasma protein concentration and/or binding do not appear to alter either the pharmacokinetics or pharmacodynamics of the drug. Consequent to a more prolonged elimination half-life for desacetylcefotaxime (e.g. approximately 1.6h in adults, 2.1h in infants and children, 9.4h in neonates) as compared to its parent drug, desacetylcefotaxime persists in plasma at concentrations which exceed the minimum concentration inhibiting 50% of organisms (MIC50) for many common paediatric pathogens for 6 to 8 hours following a cefotaxime dose. This property, coupled with excellent stability against many types of β-lactamases, produces an additive and/or synergistic antimicrobial effect when cefotaxime is used to treat infections caused by many common pathogens. Accordingly, the unique pharmacokinetic and pharmacodynamic properties of desacetylcefotaxime enable, in part, an enhanced therapeutic profile for its parent drug which may permit longer dosing intervals for cefotaxime (i.e. every 8 or 12h) to be used without necessarily compromising efficacy associated with conventional (i.e. every 6h) dosing regimens.

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  1. Department of Pediatrics, University of Arkansas for Medical Sciences and the Section on Pediatric Clinical Pharmacology, Arkansas Children’s Hospital, 800 Marshall Street, Little Rock, Arkansas, 72202, USA

    Gregory L. Kearns

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Kearns, G.L. Desacetylcefotaxime. Drug Invest 4 (Suppl 2), 9–17 (1992). https://doi.org/10.1007/BF03258352

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