Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals

Palma, Eduardo C.; Laureano, João Víctor; Araújo, Bibiana Verlindo de; Meinhardt, Nelson Guardiola; Stein, Airton Tetelbom; Costa, Teresa Dalla

doi:10.1002/bmc.4254

Cited by 10 publications

(2 citation statements)

References 34 publications

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“…The influence of several other factors has been studied as well, but the influence on protein binding was not present or not relevant. For cefazolin several studies investigated whether there was a differences between (morbidly) obese and non—obese patients ( Van Kralingen et al, 2011 ; Hites et al, 2016 ; Palma et al, 2018 ; Dorn et al, 2019 ). It was concluded that obesity did not influence protein binding.…”

Section: Resultsmentioning

confidence: 99%

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review

Jongmans

Muller²,

Broek³

et al. 2022

Front. Pharmacol.

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Introduction: Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic literature review was to give an overview of the current knowledge of protein binding of cephalosporins in human body fluids as well as to describe patient characteristics influencing the level of protein binding.Method: A systematic literature search was performed in Embase, Medline ALL, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials with the following search terms: “protein binding,” “beta-lactam antibiotic,” and “body fluid.” Only studies were included where protein binding was measured in humans in vivo.Results: The majority of studies reporting protein binding were performed in serum or plasma. Other fluids included pericardial fluid, blister fluid, bronchial secretion, pleural exudate, wound exudate, cerebrospinal fluid, dialysate, and peritoneal fluid. Protein binding differs between diverse cephalosporins and between different patient categories. For cefazolin, ceftriaxone, cefpiramide, and cefonicid a non-linear pattern in protein binding in serum or plasma was described. Several patient characteristics were associated with low serum albumin concentrations and were found to have lower protein binding compared to healthy volunteers. This was for critically ill patients, dialysis patients, and patients undergoing cardiopulmonary bypass during surgery. While mean/median percentages of protein binding are lower in these patient groups, individual values may vary considerably. Age is not likely to influence protein binding by itself, however limited data suggest that lower protein binding in newborns. Obesity was not correlated with altered protein binding.Discussion/Conclusion: Conclusions on protein binding in other body fluids than blood cannot be drawn due to the scarcity of data. In serum and plasma, there is a large variability in protein binding per cephalosporin and between different categories of patients. Several characteristics were identified which lead to a lower protein binding. The finding that some of the cephalosporins display a non-linear pattern of protein binding makes it even more difficult to predict the unbound concentrations in individual patients. Taken all these factors, it is recommended to measure unbound concentrations to optimize antibiotic exposure in individual patients.Systematic Review Registration: PROSPERO, identifier (CRD42021252776).

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Section: Resultsmentioning

confidence: 99%

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review

Jongmans

Muller²,

Broek³

et al. 2022

Front. Pharmacol.

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“…The application of the HPLC methods for the measurement of antibiotic concentrations in biological samples in clinical microbiology laboratories have been reported by White (54). Developed chromatographic methods for the determination of antibiotics in biological materials are characterized by different types of detection, such as high-performance liquid chromatography (HPLC) methods with an electrochemical detection (ECD) (55), fluorescence detection (FLD) (56)(57)(58)(59)(60), ultraviolet (UV) detection (61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77) and mass spectrometry (MS) detection (78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97).…”

Section: Methods Of Quantifying Antibiotics In Biological Samplesmentioning

confidence: 99%

Methods for Determination of Meropenem Concentration in Biological Samples

Rančić

2022

Serbian Journal of Experimental and Clinical Research

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Measuring the concentration of antibiotics in biological samples allow implementation of therapeutic monitoring of these drugs and contribute to the adjustment of the dosing regimen in patients. This increases the effectiveness of antimicrobial therapy, reduces the toxicity of these drugs and prevents the development of bacterial resistance. This review article summarizes current knowledge on methods for determining concentration of meropenem, an antibiotic drug from the group of carbapenems, in different biological samples. It provides a brief discussion of the chemical structure, physicochemical and pharmacokinetic properties of meropenem, different sample preparation techniques, use of apparatus and equipment, knowledge of the advantages and limitations of available methods, as well as directions in which new methods should be developed. This review should facilitate clinical laboratories to select and apply one of the established methods for measuring of meropenem, as well as to provide them with the necessary knowledge to develop new methods for quantification of meropenem in biological samples according to their needs.

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A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices

O'Hanlon,

Holford,

Anderson

et al. 2024

CPT Pharmacom & Syst Pharma

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Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta‐lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An ex vivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using Bmax (binding capacity), Kd (dissociation constant), and T2off (half‐time of dissociation), described cefazolin adsorption. Bmax estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ Kd estimate was 139 mg/L (95% CI 27.0, 283) and the T2off estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with Kd and T2off estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The Bmax was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. This framework could be extended to other PK studies involving CPB.

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Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals

Cited by 10 publications

References 34 publications

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review

Methods for Determination of Meropenem Concentration in Biological Samples

A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices

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