Teicoplanin Population Pharmacokinetic Analysis in Hospitalized Patients

Soy, Dolors; López, Elena Sánchez; Ribas, J.

doi:10.1097/01.ftd.0000249942.14145.ff

Cited by 32 publications

(33 citation statements)

References 33 publications

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“…Age, body weight, creatinine clearance and serum albumin concentration can be factors that affect teicoplanin pharmacokinetic according to teicoplanin population pharmacokinetic analyses. [11][12][13] However, Pea et al reported by a multivariate analysis that the weight-adjusted dose (mg/kg), but not creatinine clearance or age, is the only significant factor that correlates with teicoplanin trough concentrations on the third day. 10) Using multiple logistic regression analysis, we also previously showed that p values were 0.046 [odds ratio (OR): 0.91, 95% confidence interval (CI): 0.82-0.99] for body weight, 0.061 (OR: 1.02, 95% CI: 0.99-1.05) for creatinine clearance and 0.592 (OR: 1.42, 95% CI: 0.39-5.3) for serum albumin concentration, indicating that only the total dose per body weight statistically significantly affected teicoplanin pharmacokinetics.…”

Section: Discussionmentioning

confidence: 99%

Development of Initial Loading Procedure for Teicoplanin in Critically Ill Patients with Severe Infections

Matsumoto

Kanazawa

Watanabe

et al. 2013

Biological & Pharmaceutical Bulletin

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Methicillin-resistant Staphylococcus aureus (MRSA) is now endemic in many hospitals. Infection with MRSA is more frequent in the intensive care unit (ICU) than in general wards. Therefore, appropriate treatments for MRSA infections will lead to good outcomes in the ICU. Teicoplanin is an anti-MRSA agent. Recently, it was recommended at a new target trough concentration of 15-30 µg/mL. However, the initial loading procedure for teicoplanin to allow it to reach the target concentration promptly remains uncertain. Therefore, this study aimed to determine the appropriate initial loading procedure for teicoplanin in critically ill patients with severe infections. We performed a retrospective study in patients given teicoplanin in the ICU in order to determine the initial loading procedure to promptly reach the target trough concentration. We then evaluated the trough concentration on the third day after commencement of teicoplanin therapy. The mean loading dose and trough concentration were 11.5±1.0 mg/kg and 18.9±5.9 µg/mL, respectively. A correlation (r=0.45, p=0.046) was shown between teicoplanin loading dose and trough concentration. The correlation equation was trough concentration=2.563·loading dose −10.672. In the cases of 11.0 and 15.0 mg/ kg for the loading dose, respectively, trough concentrations were 17.5 and 27.8 µg/mL. We suggested that an initial loading dose of 11-15 mg/kg every 12 h for 3 doses should be administered to promptly achieve the target trough concentration of 15-30 µg/mL on the third day after commencement of teicoplanin therapy in the ICU.

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Section: Discussionmentioning

confidence: 99%

Development of Initial Loading Procedure for Teicoplanin in Critically Ill Patients with Severe Infections

Matsumoto

Kanazawa

Watanabe

et al. 2013

Biological & Pharmaceutical Bulletin

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“…First-order conditional estimation with the interaction approach was used throughout the modelbuilding process. Teicoplanin concentration data were log transformed for analysis and were assumed to follow a two-compartment model with first-order elimination on the basis of the findings of previous studies (14,25,(32)(33)(34). The PK parameters estimated included clearance from the central compartment (CL), the central volume of distribution (V 1 ), the peripheral volume of distribution (V 2 ), and intercompartmental (central-peripheral) clearance (Q).…”

Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

Noh

Min

et al. 2017

Antimicrob Agents Chemother

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The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a Ͼ50% probability of target attainment at 72 h using a trough concentration target of Ͼ10 g/ml for mild to moderate infections and a trough concentration target of Ͼ15 g/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

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“…5, 6 Matsumoto et al suggested a target AUC 24 /MIC ratio of ࣙ900. [14][15][16][17] Therefore, an optimal loading dose is necessary to promptly achieve the target C min (>15 mg/L), 8,9,18,19 but the standard dose (400 mg of teicoplanin twice a day as a loading dose at day 1 and 400 mg once a day as the maintenance dose) is insufficient to obtain the target concentration. [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.…”

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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.…”

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confidence: 99%

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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Teicoplanin Population Pharmacokinetic Analysis in Hospitalized Patients

Cited by 32 publications

References 33 publications

Development of Initial Loading Procedure for Teicoplanin in Critically Ill Patients with Severe Infections

Development of Initial Loading Procedure for Teicoplanin in Critically Ill Patients with Severe Infections

Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

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

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