Population pharmacokinetics of teicoplanin in hospitalized elderly patients using cystatin C as an indicator of renal function

Kasai, Hidefumi; Tsuji, Yasuhiro; Hiraki, Yoichi; Tsuruyama, Moeko; To, Hideto; Yamamoto, Yoshihiro

doi:10.1016/j.jiac.2017.12.002

Cited by 17 publications

(26 citation statements)

References 49 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: 55%

“…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%

“…The PK model of teicoplanin was described with a 2-compartment model, whereas previous studies have used 1-, 2-, or 3-compartment models. 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). Two-and 1-compartment models were evaluated, but the OFV of the 2-compartment model was significantly lower than that of the 1compartment model ( OFV 79.0, df 3, P < .05).…”

Section: Discussionmentioning

confidence: 99%

“…23 The production of CRP is promoted by inflammation associated with infection, and CRP concentrations in serum increase quickly at the beginning of infections and decrease on their alleviation. 14,15,25 However, there has been no study that has evaluated the population PKPD of teicoplanin and CRP based on data from a large-scale population. 24 A population PKPD model for predicting sequential variations of teicoplanin and CRP concentration that can be applied to a wide range of patients including the elderly, the obese, and those with renal insufficiency could provide physicians with useful information for setting individual dosing regimens.…”

mentioning

confidence: 99%

“…24 A population PKPD model for predicting sequential variations of teicoplanin and CRP concentration that can be applied to a wide range of patients including the elderly, the obese, and those with renal insufficiency could provide physicians with useful information for setting individual dosing regimens. 14,15,25 However, there has been no study that has evaluated the population PKPD of teicoplanin and CRP based on data from a large-scale population. The aims of the present study were (1) to evaluate the variability in the PK of teicoplanin by use of population PK approaches, (2) to explore the best predictor of allometric size and to evaluate the influence of renal function on the PK of teicoplanin, and (3) to develop a population PK and PD model targeting a large-scale population that would allow prediction of sequential variations of teicoplanin and CRP concentrations.…”

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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: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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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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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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Teicoplanin physiologically based pharmacokinetic modeling offers a quantitative assessment of a theoretical influence of serum albumin and renal function on its disposition

Emoto

Johnson²,

Yamada

et al. 2021

Eur J Clin Pharmacol

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Population pharmacokinetics of teicoplanin in hospitalized elderly patients using cystatin C as an indicator of renal function

Cited by 17 publications

References 49 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

Teicoplanin physiologically based pharmacokinetic modeling offers a quantitative assessment of a theoretical influence of serum albumin and renal function on its disposition

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