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Development of a Novel Multipenicillin Assay and Assessment of the Impact of Analyte Degradation: Lessons for Scavenged Sampling in Antimicrobial Pharmacokinetic Study Design.
Kipper, Karin; Barker, Charlotte I S; Standing, Joseph F; Sharland, Mike; Johnston, Atholl.
Afiliación
  • Kipper K; Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's University of London, London, United Kingdom karin.kipper@gmail.com.
  • Barker CIS; University of Tartu, Institute of Chemistry, Tartu, Estonia.
  • Standing JF; Analytical Services International Ltd., St. George's University of London, London, United Kingdom.
  • Sharland M; Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's University of London, London, United Kingdom.
  • Johnston A; Inflammation, Infection and Rheumatology Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
Article en En | MEDLINE | ID: mdl-29084754
Penicillins are widely used to treat infections in children; however, the evidence is continuing to evolve in defining the optimal dosing. Modern pediatric pharmacokinetic study protocols frequently favor opportunistic, "scavenged" sampling. This study aimed to develop a small-volume single assay for five major penicillins and to assess the influence of sample degradation on inferences made using pharmacokinetic modeling, to investigate the suitability of scavenged sampling strategies. Using a rapid ultrahigh-performance liquid chromatographic-tandem mass spectrometric method, an assay for five penicillins (amoxicillin, ampicillin, benzylpenicillin, piperacillin, and flucloxacillin) in blood plasma was developed and validated. Penicillin stabilities were evaluated under different conditions. Using these data, the impact of drug degradation on inferences made during pharmacokinetic modeling was evaluated. All evaluated penicillins indicated good stability at room temperature (23 ± 2°C) over 1 h, remaining in the range of 98 to 103% of the original concentration. More-rapid analyte degradation had already occurred after 4 h, with stability ranging from 68% to 99%. Stability over longer periods declined: degradation of up to 60% was observed with delayed sample processing of up to 24 h. Modeling showed that analyte degradation can lead to a 30% and 28% bias in clearance and volume of distribution, respectively, and falsely show nonlinearity in clearance. Five common penicillins can now be measured in a single low-volume blood sample. Beta-lactam chemical instability in plasma can cause misleading pharmacokinetic modeling results, which could impact upon model-based dosing recommendations and the forthcoming era of beta-lactam therapeutic drug monitoring.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Penicilina G / Piperacilina / Floxacilina / Amoxicilina / Ampicilina / Antibacterianos Tipo de estudio: Guideline Límite: Humans Idioma: En Revista: Antimicrob Agents Chemother Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Penicilina G / Piperacilina / Floxacilina / Amoxicilina / Ampicilina / Antibacterianos Tipo de estudio: Guideline Límite: Humans Idioma: En Revista: Antimicrob Agents Chemother Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido