Can capillary microsampling facilitate a clinical pharmacokinetics study of cefazolin in critically ill children?

Pharmacokinetic studies in children are limited, in part due to challenges in blood sampling. We compare the use of capillary microsampling and conventional sampling techniques in pediatric patients to show results that can be used in the pharmacokinetic analysis of Cefazolin. Paired blood samples (n = 48) were collected from 12 patients (median age/weight 49 months/18 kg).

Optimal dosing of cefotaxime and desacetylcefotaxime for critically ill paediatric patients. Can we use microsampling?

Objectives: To describe the population pharmacokinetics of cefotaxime and desacetylcefotaxime in critically ill paediatric patients and provide dosing recommendations. We also sought to evaluate the use of capillary microsampling to facilitate data-rich blood sampling.

Methods: Patients were recruited into a pharmacokinetic study, with cefotaxime and desacetylcefotaxime concentrations from plasma samples collected at 0, 0.

Development and validation of a UHPLC-MS/MS method to measure cefotaxime and metabolite desacetylcefotaxime in blood plasma: a pilot study suitable for capillary microsampling in critically ill children.

Critical illness has been shown to affect the pharmacokinetics of antibiotics, which can lead to ineffective antibiotic exposure and the potential emergence of resistant bacteria. The lack of studies describing antibiotic pharmacokinetics in critically ill children has led to significant off-label dosing. This is, in part, due to the ethical and physiological challenges of removing frequent, large-volume samples from children.

Microsampling to support pharmacokinetic clinical studies in pediatrics.

Background: Conventional sampling for pharmacokinetic clinical studies requires removal of large blood volumes from patients. This can result in a physiological/emotional burden for children. Microsampling to support pharmacokinetic clinical studies in pediatrics may reduce this burden.

Pharmacodynamics of once- versus twice-daily dosing of nebulized amikacin in an in vitro Hollow-Fiber Infection Model against 3 clinical isolates of Pseudomonas aeruginosa.

This study aims to compare the bacterial killing of once- versus twice-daily nebulized amikacin against Pseudomonas aeruginosa and to determine the optimal duration of therapy. Three clinical P. aeruginosa isolates (amikacin MICs 2, 8, and 64 mg/L) were exposed to simulated epithelial lining fluid exposures of nebulized amikacin with dosing regimens of 400 mg and 800 mg once- or twice-daily up to 7-days using the in vitro hollow-fiber infection model.

Pharmacodynamic Evaluation of Plasma and Epithelial Lining Fluid Exposures of Amikacin against Pseudomonas aeruginosa in a Dynamic Hollow-Fiber Infection Model.

Given that aminoglycosides, such as amikacin, may be used for multidrug-resistant infections, optimization of therapy is paramount for improved treatment outcomes. This study aims to investigate the pharmacodynamics of different simulated intravenous amikacin doses on susceptible to inform ventilator-associated pneumonia (VAP) and sepsis treatment choices. A hollow-fiber infection model with two isolates (MICs of 2 and 8 mg/liter) with an initial inoculum of ∼10 CFU/ml was used to test different amikacin dosing regimens.

In-vitro adsorption and sieving coefficient of ticarcillin-clavulanate during continuous haemofiltration.

There are very limited data on ticarcillin-clavulanate elimination by haemofiltration. We measured in vitro ticarcillin-clavulanate adsorption to polyacrylonitrile (PAN) filters and the sieving coefficient using a well-described bench model of haemofiltration. The dose of ticarcillin-clavulanate was 60/2 mg or 180/3 mg, and 0 or 12 g albumin was added to the 1 L of circulating blood-crystalloid mixture to produce four different experimental conditions.

Analysis of capillary microsamples obtained from a skin-prick to measure vancomycin concentrations as a valid alternative to conventional sampling: A bridging study.

A bridging study is presented to investigate the applicability of measuring vancomycin concentrations obtained by finger-prick. A total of 25 paired plasma samples, collected from finger prick as capillary microsampling and arterial plasma samples collected from an indwelling cannula as conventional sampling, were obtained from critically ill patients receiving vancomycin. The maximum concentration (C) and the minimum concentration (C) measured were 66.

Clinical application of microsampling versus conventional sampling techniques in the quantitative bioanalysis of antibiotics: a systematic review.

Conventional sampling techniques for clinical pharmacokinetic studies often require the removal of large blood volumes from patients. This can result in a physiological or emotional burden, particularly for neonates or pediatric patients. Antibiotic pharmacokinetic studies are typically performed on healthy adults or general ward patients.

A UHPLC-MS/MS method for the simultaneous determination of piperacillin and tazobactam in plasma (total and unbound), urine and renal replacement therapy effluent.

Piperacillin-tazobactam is a beta-lactam/beta-lactamase combination antibiotic used in patients with moderate to severe infection. Dosing of piperacillin-tazobactam requires an understanding of this patient group to maximise the effectiveness of this antibiotic and limit a further emergence of resistant pathogens. This is the first method that measures piperacillin and tazobactam simultaneously, across this range of clinically-relevant biological matrices.

A validated UHPLC-MS/MS method for the measurement of riluzole in plasma and myocardial tissue samples.

Through blocking the cardiac persistent sodium current, riluzole has the potential to prevent myocardial damage post cardiac bypass surgery. A sensitive UHPLC-MS/MS method was developed and validated for quantitation of riluzole and 5-methoxypsoralen in human plasma and myocardial tissue homogenate using a liquid-liquid extraction with dichloromethane. The chromatographic separation was achieved using Shimadzu Shim-pack XR-ODS III, 2.

An LC-MS/MS method to determine vancomycin in plasma (total and unbound), urine and renal replacement therapy effluent.

Aim: Critical illness and medical interventions, such as renal replacement therapy, can cause changes to vancomycin pharmacokinetics and lead to suboptimal dosing. To comprehensively characterize vancomycin pharmacokinetic a method must measure vancomycin in a range of clinical matrices.

Results: A LC-MS/MS method was developed using hydrophilic interaction liquid chromatography and microsample volumes, where possible.

Effect of time on recovery of plasma microsamples for the quantitative determination of vancomycin.

The reliability of extraction recovery of an analyte in bioanalysis is fundamentally important for downstream analytical testing. For dried format microsamples, if the recovery changes with time the concentration in clinical samples, derived from calibration standards and alongside quality control samples prepared following different drying protocols, may not reflect the true result. The purpose of this paper was therefore to evaluate changes to extraction recovery across time for one analyte, the glycopeptide antibiotic vancomycin, in plasma using two dried microsampling formats, dried plasma spots and volumetric absorptive microsampling.

Determination of Cefalothin and Cefazolin in Human Plasma, Urine and Peritoneal Dialysate by UHPLC-MS/MS: application to a pilot pharmacokinetic study in humans.

An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the analysis of cefazolin and cefalothin in human plasma (total and unbound), urine and peritoneal dialysate has been developed and validated. Total plasma concentrations are measured following protein precipitation and are suitable for the concentration range of 1-500 µg/mL. Unbound concentrations are measured from ultra-filtered plasma acquired using Centrifree(®) devices and are suitable for the concentration range of 0.

High-throughput assay for simultaneous quantification of the plasma concentrations of morphine, fentanyl, midazolam and their major metabolites using automated SPE coupled to LC-MS/MS.

A rapid LC-MS/MS assay method for simultaneous quantification of morphine, fentanyl, midazolam and their major metabolites: morphine-3-β-D-glucuronide (M3G), morphine-6-β-D-glucuronide (M6G), norfentanyl, 1'-hydroxymidazolam (1-OH-MDZ) and 4-hydroxymidazolam (4-OH-MDZ) in samples of human plasma has been developed and validated. Robotic on-line solid phase extraction (SPE) instrumentation was used to elute the eight analytes of interest from polymeric SPE cartridges to which had been added aliquots (150 μL) of human plasma and aliquots (150 μL) of a mixture of two internal standards, viz. morphine-d3 (200 ng/mL) and 1'-hydroxymidazolam-d5 (50 ng/mL) in 50 mM ammonium acetate buffer (pH 9.