Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DALI Study

Antonino Giarratano, Santi Maurizio Raineri, Andrea Cortegiani, Francesca Montalto, Maria Teresa Strano

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Abstract

The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10–30mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2–26.0) and free 1.5 (0.7–2.5); trough, total 11.9 (10.2–22.7) and free 1.8 (0.6–2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5–15.6%) and 8.2% (5.5–16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint ( = 0.79, P = 0.0021) and trough (= 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concen- trations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.
Lingua originaleEnglish
pagine (da-a)423-430
Numero di pagine8
RivistaInternational Journal of Antimicrobial Agents
Volume43
Stato di pubblicazionePublished - 2014

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Teicoplanin
Drug Monitoring
Protein Binding
Critical Illness
Therapeutics
Pharmacokinetics
Anti-Bacterial Agents

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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title = "Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DALI Study",
abstract = "The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10–30mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2–26.0) and free 1.5 (0.7–2.5); trough, total 11.9 (10.2–22.7) and free 1.8 (0.6–2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9{\%} (4.5–15.6{\%}) and 8.2{\%} (5.5–16.4{\%}), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint ( = 0.79, P = 0.0021) and trough (= 0.63, P = 0.027). Only 42{\%} and 58{\%} of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concen- trations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.",
author = "Antonino Giarratano and Raineri, {Santi Maurizio} and Andrea Cortegiani and Francesca Montalto and Strano, {Maria Teresa}",
year = "2014",
language = "English",
volume = "43",
pages = "423--430",
journal = "International Journal of Antimicrobial Agents",
issn = "0924-8579",
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T1 - Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DALI Study

AU - Giarratano, Antonino

AU - Raineri, Santi Maurizio

AU - Cortegiani, Andrea

AU - Montalto, Francesca

AU - Strano, Maria Teresa

PY - 2014

Y1 - 2014

N2 - The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10–30mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2–26.0) and free 1.5 (0.7–2.5); trough, total 11.9 (10.2–22.7) and free 1.8 (0.6–2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5–15.6%) and 8.2% (5.5–16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint ( = 0.79, P = 0.0021) and trough (= 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concen- trations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.

AB - The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10–30mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2–26.0) and free 1.5 (0.7–2.5); trough, total 11.9 (10.2–22.7) and free 1.8 (0.6–2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5–15.6%) and 8.2% (5.5–16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint ( = 0.79, P = 0.0021) and trough (= 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concen- trations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.

UR - http://hdl.handle.net/10447/96407

M3 - Article

VL - 43

SP - 423

EP - 430

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

SN - 0924-8579

ER -