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Validation and Application of an HPLC-DAD Method for Routine Therapeutic Drug Monitoring of Ceftobiprole.

ABSTRACT: Ceftobiprole is a fifth-generation cephalosporin approved for the treatment of pneumonia, with a broad antibacterial spectrum, including potent activity against methicillin-resistant Staphylococcus aureus As for the other cephalosporins, high pharmacokinetic variability and concentration-dependent neurotoxicity are expected. We describe here the first simple and rapid analytical method intended for ceftobiprole serum concentration monitoring. We report the data of 5 patients treated with ceftobiprole, among who 2 developed reversible neurological disorders with high ceftobiprole serum concentration.

SUBMITTER: Lima B

PROVIDER: S-EPMC6591631 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Validation and Application of an HPLC-DAD Method for Routine Therapeutic Drug Monitoring of Ceftobiprole.

Lima Benjamin B Bodeau Sandra S Quinton Marie-Charlotte MC Leven Cyril C Lemaire-Hurtel Anne-Sophie AS Bennis Youssef Y

Antimicrobial agents and chemotherapy 20190624 7

Ceftobiprole is a fifth-generation cephalosporin approved for the treatment of pneumonia, with a broad antibacterial spectrum, including potent activity against methicillin-resistant <i>Staphylococcus aureus</i> As for the other cephalosporins, high pharmacokinetic variability and concentration-dependent neurotoxicity are expected. We describe here the first simple and rapid analytical method intended for ceftobiprole serum concentration monitoring. We report the data of 5 patients treated with ...[more]

PMID: 31010863

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Project description:BackgroundIn-hospital therapeutic drug monitoring (TDM) requires a suitable quantification method for target drugs from the viewpoint of precision, throughput, and testing costs. We previously developed a practical HPLC-UV platform for quantification of serum levels of various drugs. In this report, the platform was effectively applied to the quantification of patient serum levels of five different drugs by clinical professionals in our hospital during their daily work.MethodsThe residual sera of patients receiving carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), vancomycin (VCM), or voriconazole (VRCZ) were used in the present clinical study. The quantification method for each drug consisted of rapid solid-phase extraction (SPE) of each drug in the patient serum, followed by optimized HPLC-UV analysis of the drug in the SPE eluate. Furthermore, patient serum levels of PHT, CBZ, and VCM were also measured by ligand-binding assay using a cobas® analyzer in our hospital, and those of LTG and VRCZ were measured by HPLC-MS/MS at an outsourced provider. Passing-Bablok regression analysis and Bland-Altman analysis were employed to analyze the agreement of drug levels in patient sera, which was separately quantified using two different methods-our HPLC-UV platform and the cobas analyzer, or HPLC-UV and HPLC-MS/MS.ResultsAll analytical conditions of the present method using our HPLC-UV platform were well optimized for each target drug quantification in the patient's serum, and the quantification method for each drug was fully validated for accuracy, precision and reproducibility. Furthermore, Passing-Bablok regression analysis and Bland-Altman analysis revealed that patient serum levels of PHT, CBZ, and VCM quantified by our HPLC-UV platform were closely correlated with those quantified by the cobas® analyzer, and the levels of LTG and VRCZ quantified by our HPLC-UV platform were also correlated with those quantified by HPLC-MS/MS.ConclusionsOur HPLC-UV platform can be performed without requiring special analytical techniques. This platform is expected to be used for the measurement of blood levels of multiple drugs for in-hospital routine TDM.

Project description:Fetal arrhythmia develops in 0.1-5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely initiation of transplacental antiarrhythmic therapy (ART) promotes the conversion of fetal tachycardia to sinus rhythm and the regression of the concomitant non-immune fetal hydrops. The optimal treatment regimen search for the fetus with tachyarrhythmia is still of high value. Polymorphisms of these genes determines the individual features of the drug pharmacokinetics. The aim of this study was to study the pharmacokinetics of transplacental anti-arrhythmic drugs in the fetal therapy of arrhythmias using HPLC-MS/MS, as well as to assess the effect of the multidrug-resistance gene ABCB1 3435C > T polymorphism on the efficacy and maternal/fetal complications of digoxin treatment. The predisposition to a decrease in the bioavailability of the digoxin in patients with a homozygous variant of the CC polymorphism showed a probable association with the development of ART side effects. A pronounced decrease in heart rate in women with the 3435TT allele of the ABCB1 gene was found. The homozygous TT variant in the fetus showed a probable association with an earlier response to ART and rhythm disruptions on the digoxin dosage reduction. high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) methods for digoxin and sotalol therapeutic drug monitoring in blood plasma, amniotic fluid, and urine were developed. The digoxin and sotalol concentrations were determined in the plasma blood, urine, and amniotic fluid of 30 pregnant women at four time points (from the beginning of the transplacental antiarrhythmic therapy to delivery) and the plasma cord blood of 30 newborns. A high degree of correlation between the level of digoxin and sotalol in maternal and cord blood was found. The ratio of digoxin and sotalol in cord blood to maternal blood was 0.35 (0.27 and 0.46) and 1.0 (0.97 and 1.07), accordingly. The digoxin concentration in the blood of the fetus at the moment of the first rhythm recovery episode, 0.58 (0.46, 0.8) ng/mL, was below the therapeutic interval. This confirms the almost complete transplacental transfer of sotalol and the significant limitation in the case of digoxin. Previously, ABCB1/P-glycoprotein had been shown to limit fetal exposure to drugs. Further studies (including multicenter ones) to clarify the genetic features of the transplacental pharmacokinetics of antiarrhythmic drugs are needed.

Dataset Information

Validation and Application of an HPLC-DAD Method for Routine Therapeutic Drug Monitoring of Ceftobiprole.

Publications

Validation and Application of an HPLC-DAD Method for Routine Therapeutic Drug Monitoring of Ceftobiprole.

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