Dalbavancin: Quantification in human plasma and urine by a new improved high performance liquid chromatography–tandem mass spectrometry method

Alebic-Kolbah, Tanja; Demers, Roger; Cojocaru, Laura

doi:10.1016/j.jchromb.2011.07.027

Cited by 26 publications

(24 citation statements)

References 6 publications

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“…Dalbavancin plasma concentrations in DUR001‐303 were measured using a high‐performance liquid chromatography‐tandem mass spectrometry bioanalytical method, validated in the linear range from 0.5 to 500 µg/mL using 50 µL of K 2 ‐ethylenediaminetetraacetic acid plasma . This was an updated version of the method details previously published, which were used in studies VER001‐4, VER001‐5, and VER001‐9.…”

Section: Methodsmentioning

confidence: 99%

Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis

Carrothers

Chittenden

Critchley

2019

Clinical Pharm in Drug Dev

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Dalbavancin is indicated for the treatment of acute bacterial skin and skin structure infections caused by susceptible gram-positive microorganisms. This analysis represents the update of the population pharmacokinetics (popPK) modeling and target attainment simulations performed with data from the single-dose safety and efficacy study and an unrelated but substantial revision of the preclinical pharmacokinetic/pharmacodynamic target (fAUC/MIC, free area under concentration-time curve/minimum inhibitory concentration ratio). A 3-compartment distribution model with first-order elimination provided an appropriate fit, with typical dalbavancin clearance of 0.05 L/h and total volume of distribution of ß15 L. Impact of intrinsic factors was modest, although statistically significant (P < .05) relationships with total clearance were found for the following covariates: creatinine clearance, weight, and albumin -dose adjustment was only indicated for severe renal impairment. Under the new nonclinical target, simulations of the popPK model projected that >99% of subjects would achieve the nonclinical target at MIC values up to and including 2 mg/L. Keywordsacute bacterial skin and skin structure infection, dalbavancin, long-acting intravenous antibiotic, pharmacokinetics, target attainment 1 Allergan plc,

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Section: Methodsmentioning

confidence: 99%

Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis

Carrothers

Chittenden

Critchley

2019

Clinical Pharm in Drug Dev

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“…Plasma and dialysate samples were processed and stored at Ϫ80°C until the completion of enrollment and sample collection. Dalbavancin concentrations in plasma and dialysate samples were determined via a previously published liquid chromatography-tandem mass spectrometry assay (20) at the University of Colorado Medicinal Chemistry Core Facility.…”

Section: Methodsmentioning

confidence: 99%

Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

Matre

Teitelbaum

Kiser

2020

Antimicrob Agents Chemother

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Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its coverage of Gram-positive bacteria and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin in a prospective, randomized, open-label, crossover PK study of adult patients with end-stage renal disease ESRD who were receiving PD. Sampling occurred prior to a single 30-min infusion of dalbavancin at 1,500 mg and at 1, 2, 3, 4, and 6 h and 7 and 14 days postadministration. Concentration-time data were analyzed via noncompartmental analysis. Pharmacodynamic parameters against common infectious peritonitis-causing pathogens were evaluated. Ten patients were enrolled. Patients were a median of 55 years old and had a median weight of 78.2 kg, 50% were female, and 70% were Caucasian. The terminal plasma half-life of dalbavancin was 181.4 ± 35.5 h. The day 0 to day 14 dalbavancin mean area under the curve (AUC) was 40,573.2 ± 9,800.3 mg·h/liter. The terminal-phase half-life of dalbavancin within the peritoneal fluid was 4.309 × 108 ± 1.140 × 109 h. The day 0 to day 14 dalbavancin mean peritoneal fluid AUC was 2,125.0 ± 1,794.3 mg·h/liter. The target plasma AUC/MIC was attained with the intravenous dose in all 10 patients for all Staphylococcus and Streptococcus species at the recommended MIC breakpoints. The intraperitoneal arm of the study was stopped early, because the first 3 patients experienced moderate to severe pain and bloating within 1 h following the administration of dalbavancin. Dalbavancin at 1,500 mg administered intravenously can be utilized without dose adjustment in peritoneal dialysis patients and will likely achieve the necessary peritoneal fluid concentrations to treat peritonitis caused by typical Gram-positive pathogens.

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“…Immediately after separation samples were stored and frozen at approximately −20 °C or below until shipment to the bioanalytical laboratory. Plasma was analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) validated for dalbavancin in the linear range from 0.5 μg/ml to 500 μg/ml using 50 μl of K2 EDTA plasma [ 16 ]. The pharmacokinetic parameters listed in this section were calculated from the plasma concentration–actual time profiles.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics, Safety, and Tolerability of a Single 500-mg or 1000-mg Intravenous Dose of Dalbavancin in Healthy Japanese Subjects

Scoble¹,

Owens²,

Puttagunta³

et al. 2015

Clin Drug Investig

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Background and ObjectivesDalbavancin is a novel, once-weekly glycopeptide antibiotic approved for treatment of acute bacterial skin infections. Given the importance of understanding any pharmacokinetic variability across different patient populations, a double-blind, placebo-controlled study was conducted to evaluate the pharmacokinetics, safety, and tolerability of a single 500-mg and a single 1000-mg intravenous dose of dalbavancin in healthy Japanese subjects.MethodsTen subjects received intravenous dalbavancin 1000 mg, five subjects received intravenous dalbavancin 500 mg, and three subjects received intravenous placebo.ResultsAfter a single infusion of dalbavancin, the maximal plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) increased in a proportional manner from 500 mg to 1000 mg (Cmax: 157 μg/ml and 299 μg/ml; AUClast: 10,850 μg·h/ml and 22,679 μg·h/ml, on the 500-mg and 1000-mg regimens, respectively) with low inter-subject variability. The mean terminal phase half-life (t1/2) was 204 and 193 h after the 500-mg and 1000-mg dose, respectively. Clearance and volume of distribution were similar for the two dose concentrations. Treatment-emergent adverse events reported were considered to be of mild intensity. There were no relevant changes in laboratory values or vital signs over time in subjects in either treatment group.ConclusionsOverall, dalbavancin 500 mg and dalbavancin 1000 mg, administered as a single 30-min infusion, was well tolerated in this population and resulted in plasma exposures similar to those in non-Asians.

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Dalbavancin: Quantification in human plasma and urine by a new improved high performance liquid chromatography–tandem mass spectrometry method

Cited by 26 publications

References 6 publications

Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis

Dalbavancin Population Pharmacokinetic Modeling and Target Attainment Analysis

Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

Pharmacokinetics, Safety, and Tolerability of a Single 500-mg or 1000-mg Intravenous Dose of Dalbavancin in Healthy Japanese Subjects

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