Population pharmacokinetics of teicoplanin administered by subcutaneous or intravenous route and simulation of optimal loading dose regimen

Cazaubon, Yoann; Venisse, Nicolas; Mimoz, Olivier; Maire, Pascal; Ducher, Michel; Bourguignon, Laurent; Goutelle, Sylvain

doi:10.1093/jac/dkx242

Cited by 30 publications

(38 citation statements)

References 28 publications

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“…F fat , included in NFM as the factor describing the influence of fat mass for CL, was not significantly different from 1, and F fat , for volume of distribution, was not significantly different from 0. 12,14,15,25,49 In the present study RF was an important covariate of CL and markedly improved model fitting ( OFV 61.7, df 1, P < .05). 32,48 Teicoplanin exhibited a hydrophilic character, and few teicoplanin distributed organic phases in a previous study.…”

Section: Discussionsupporting

confidence: 56%

“…12,[14][15][16]25,46,47 The teicoplanin concentrations were mainly collected in the elimination phase, with some being from the distribution phase (Figure 1). 12,[14][15][16]25,46,47 The teicoplanin concentrations were mainly collected in the elimination phase, with some being from the distribution phase (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Several doses (loading doses 400-800 mg or 10-15 mg/kg and maintenance dose 200-800 mg or 5-15 mg/kg) were selected based on the standard dosing regimen and the recommendation in previous studies, [10][11][12][13] and the probabilities of reaching the target C min (15-30 mg/L) at days 1, 3, and 7 in 1000 virtual patients were compared. One thousand virtual patients were randomly generated by uniform random numbers based on 95% observation intervals of patients in the popPK analysis (TBW 34-90 kg, height 139-176 m, CLcr 1.1-10.4 L/h) using R 3.5.0 (Vienna, Austria).…”

Section: Population Pkpd Simulationmentioning

confidence: 99%

“…4 The clinical benefit of teicoplanin is associated with the ratio of the area under the drug concentrationtime curve (AUC) to the minimum inhibitory concentration (MIC). [8][9][10][11][12][13] Teicoplanin has a long elimination half-life (>30 hours), which leads to prolongation of the time needed to achieve a steady state. 6 The use of therapeutic drug monitoring has been recommended with a target minimum concentration (C min ) range of 15-30 mg/L, 7 but the optimal dosing regimen is not yet known.…”

mentioning

confidence: 99%

“…[8][9][10][11][12][13] Teicoplanin has a long elimination half-life (>30 hours), which leads to prolongation of the time needed to achieve a steady state. [10][11][12][13] Assessment of clinical efficacy in patients with infections is usually based on the serum concentrations of C-reactive protein (CRP). 9,20 Recently, a higher loading dose (ࣙ600 mg) and dose adjustment based on the total body weight (ࣙ10 mg/kg) have been recommended to quickly achieve the target C min .…”

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confidence: 99%

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Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C‐Reactive Protein in Hospitalized Patients With Gram‐Positive Infections

Ogami

Tsuji

Mizoguchi

et al. 2019

Clinical Pharm in Drug Dev

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Teicoplanin is an antibiotic agent used for the treatment of Gram-positive infections. The clinical benefit of teicoplanin is associated with its blood concentrations, but the optimal dosing regimen is not yet known. To explore the optimal individual dosing regimen, we performed a population pharmacokinetic (PK) and pharmacodynamic (PD) analysis targeting a large-scale population, including patients with a wide range of ages, body weights, and renal functions. The PK of teicoplanin was described with a 2-compartment model, and the PD of C-reactive protein (CRP) concentrations was described with a turnover maximum inhibition model. The elimination half-life of teicoplanin calculated from the final estimated parameters was 169 hours, and renal function was a significant covariate of teicoplanin clearance. The teicoplanin concentration producing 50% of the maximum inhibition of CRP production was estimated to be 2.66 mg/L. The minimum concentration of teicoplanin in patients with higher loading doses (15 mg/kg) reached the target range (15-30 mg/L) with a probability of >50% in the dosing simulation. We described the influence of body size, body composition, and renal function on the PK of teicoplanin. The population PKPD model of teicoplanin and CRP in this study should provide useful information for development of a dosing strategy including the sequential clinical benefit of teicoplanin. KeywordsC-reactive protein, pharmacodynamics, pharmacokinetics, teicoplanin, therapeutic drug monitoring Teicoplanin, a glycopeptide antibiotic agent first approved in France and Italy in 1988, is currently available and used in over 60 countries for the treatment of Gram-positive infections including methicillinresistant Staphylococcus aureus. 1 Teicoplanin has a structure and a mechanism similar to those of vancomycin, another glycopeptide antibacterial agent, and exhibits bactericidal activity by inhibiting the synthesis of cell wall peptidoglycan. 2 A meta-analysis study comparing the efficacy and toxicity of teicoplanin and vancomycin revealed no significant differences in efficacy between these 2 drugs, but adverse events (eg,

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Population Pkpd Simulationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C‐Reactive Protein in Hospitalized Patients With Gram‐Positive Infections

Ogami

Tsuji

Mizoguchi

et al. 2019

Clinical Pharm in Drug Dev

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Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment

Lin

Chen

et al. 2021

The Journal of Clinical Pharma

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The pharmacokinetics of teicoplanin differs in children as compared with adults, and especially in renally impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment-related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with a <1.36-fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration-time curve was predicted to increase 1.25fold, 1.95-fold, and 2.82-fold in pediatric patients with mild, moderate, and severe renal impairment, respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12-hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild, moderate, and severe renal impairment, respectively, at a susceptible minimum inhibitory concentration <2 mg/L. In conclusion, our PBPK model with an incorporated Monte Carlo simulation can provide improved guidance on dosing in pediatric patients with differing renal function and provide a basis for precision therapy with teicoplanin.

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Efficacy of teicoplanin monotherapy following initial standard therapy in Enterococcus faecalis infective endocarditis: a retrospective cohort study

Nadaï¹,

François²,

Sommet³

et al. 2019

Infection

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Population pharmacokinetics of teicoplanin administered by subcutaneous or intravenous route and simulation of optimal loading dose regimen

Cited by 30 publications

References 28 publications

Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C‐Reactive Protein in Hospitalized Patients With Gram‐Positive Infections

Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C‐Reactive Protein in Hospitalized Patients With Gram‐Positive Infections

Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment

Efficacy of teicoplanin monotherapy following initial standard therapy in Enterococcus faecalis infective endocarditis: a retrospective cohort study

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