Microanalysis of amoxicillin, flucloxacillin, and rifampicin in neonatal plasma

Pullen, Joyce; Stolk, L. M. L.; Neef, Cees; Zimmermann, Luc J. I.

doi:10.1002/bmc.881

Cited by 13 publications

(8 citation statements)

References 26 publications

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“…The relationship between plasma concentration and sd was fitted with a polynomial of second order [14]. With this polynomial the lower limit of quantification with a precision of 20% has been calculated and was 0.8 mg/L [15]. All our measured concentrations were above 0.8 mg/L.…”

Section: Methodsmentioning

confidence: 99%

Is the standard dose of amoxicillin-clavulanic acid sufficient?

Haeseker

Havenith

Stolk

et al. 2014

BMC Pharmacol Toxicol

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BackgroundThe pharmacodynamic (PD) efficacy target of amoxicillin is 40% time above the minimal inhibition concentration (40%T > MIC). Recent studies of other antibiotics have shown that PD-efficacy targets are not always reached. The aim of this study was to evaluate the percentage of hospitalised patients, using amoxicillin/clavulanic acid intravenously (iv), that reach the pharmacodynamic efficacy target 40%T > MIC. Additionally, the association of demographic anthropomorphic and clinical parameters with the pharmacokinetics and pharmacodynamics of amoxicillin were determined.MethodsIn serum of 57 hospitalised patients amoxicillin concentrations were measured using high performance liquid chromatography. Patients were older than 18 years and most patients had an abdominal infection. The standard amoxicillin/clavulanic acid dose was 4 times a day 1000/200 mg iv. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\Pharm 3.60). A one-compartment open model was used. Individual dosing simulations were performed with MW\Pharm.ResultsIn our study population, the mean (±SD) age was 67 (±16) years and the mean clearance corrected for bodyweight was 0.17 (±0.07) L/h/kg. Only, 65% of the patients reached the proposed amoxicillin 40%T > MIC with amoxicillin/clavulanic acid for bacterial MICs of 8 mg/L. A computer simulated increase of the standard dose to 6 times daily, increased this percentage to 95%. In this small study group 40%T > MIC was not associated with clinical or microbiological cure.ConclusionA substantial proportion of the hospitalised patients did not reach the 40%T > MIC with the standard dose amoxicillin/clavulanic acid for a bacterial MIC of 8 mg/L. Therefore, we suggest increasing the standard dose of amoxicillin/clavulanic acid to 6 times a day in patients with severe Enterobacteriaceae infections.Trial registrationTrial registration number: NTR1725 16th march 2009.

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Section: Methodsmentioning

confidence: 99%

Is the standard dose of amoxicillin-clavulanic acid sufficient?

Haeseker

Havenith

Stolk

et al. 2014

BMC Pharmacol Toxicol

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“…In addition, the efficiency of trials in which multiple drugs are administered is greatly increased because multiple assay validations are not necessary . Multiplex assays with ultralow volumes have been used to characterize the PK of multiple drugs, including acetaminophen, caffeine, phenytoin, and several antimicrobials, among others …”

Section: Clinical Trial Optimizationmentioning

confidence: 99%

Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children

Balevic

Cohen‐Wolkowiez

2018

The Journal of Clinical Pharma

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Almost half of recent pediatric trials failed to achieve labeling indications, due in large part to inadequate study design. Therefore, innovative study methods are crucial to optimize trial design while also reducing the potential harms inherent with drug investigation. Several methods exist to optimize the amount of pharmacokinetic (PK) data collected from the smallest possible volume and with the fewest number of procedures, including the use of opportunistic and sparse sampling, alternative and non-invasive matrices, and micro-volume assays. In addition, large research networks using master protocols promote collaboration, reduce regulatory burden, and increase trial efficiency for both early- and late-phase trials. Large pragmatic trials that leverage electronic health records can capitalize on central management strategies to reduce costs, enroll patients with rare diseases on a large scale, and augment study generalizability. Further, trial efficiency and safety can be optimized through Bayesian adaptive techniques that permit planned protocol changes based on analyses of prior and accumulated data. In addition to these trial design features, advances in modeling and simulation have paved the way for systems-based and physiologically-based models that individualize pediatric dosing recommendations and support drug approval. Lastly, given the low prevalence of many pediatric diseases, collecting de-identified genetic and clinical data on a large scale is a potentially transformative way to augment clinical pharmacology research in children.

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“…For analysis of unstable drugs, the main challenge is how to keep the drug stable during sample preparation. Many bioanalytical methods have been reported for the determination of the two analytes, including liquid chromatography (LC) coupled to fluorescence detection (Mascher and Kikuta, ), LC with UV detection (Charles and Chulavatnatol, ; Lindegardh et al ., ; Pullen et al ., ) and LC‐mass spectrometry (LC‐MS; Yoon et al ., ; Baglie et al ., ) for AMO, and LC‐MS (Su et al ., ) and LC‐MS/MS (Kim et al ., ; Hang et al ., ; Lin and Chen, ; Hu et al ., ) for ambroxol. However, only one method (Wen et al ., ) has been established for simultaneous determination of these two drugs, in which the unstable problem of AMO in plasma was not investigated.…”

Section: Introductionmentioning

confidence: 99%

A sensitive LC‐MS/MS method for the simultaneous determination of amoxicillin and ambroxol in human plasma with segmental monitoring

Dong

Ding

Cao

et al. 2012

Biomedical Chromatography

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Amoxicillin (AMO) degrades in plasma at room temperature and readily undergoes hydrolysis by the plasma amidase. In this paper, a novel, rapid and sensitive LC-MS/MS method operated in segmental and multiple reaction monitoring has been developed for the simultaneous determination of amoxicillin and ambroxol in human plasma. The degradation of amoxicillin in plasma was well prevented by immediate addition of 20 μL glacial acetic acid to 200 μL aliquot of freshly collected plasma samples before storage at -80°C. The sensitivity of the method was improved with segmental monitoring of the analytes, and lower limits of quantitation of 0.5 ng/mL for ambroxol and 5 ng/mL for amoxicillin were obtained. The sensitivity of our method was five times better than those of the existing methods. Furthermore, the mass response saturation problem with amoxicillin was avoided by diluting the deproteinized plasma samples with water before injection into the LC-MS/MS system. The method was successfully employed in a pharmacokinetic study of the compound amoxicillin and ambroxol hydrochloride tablets.

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Microanalysis of amoxicillin, flucloxacillin, and rifampicin in neonatal plasma

Cited by 13 publications

References 26 publications

Is the standard dose of amoxicillin-clavulanic acid sufficient?

Is the standard dose of amoxicillin-clavulanic acid sufficient?

Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children

A sensitive LC‐MS/MS method for the simultaneous determination of amoxicillin and ambroxol in human plasma with segmental monitoring

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