Population pharmacokinetics and model-based dosing optimization of teicoplanin in elderly critically ill patients with pneumonia

Sung Wook Kang, Hyeong Geun Jo, Donghyun Kim, Kyeoul Jeong, Jaeok Lee, Hwa Jeong Lee, Seungwon Yang, Sohyun Park, Sandy Jeong Rhie, Eun Kyoung Chung

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Abstract

Purpose: To evaluate the population pharmacokinetics and pharmacodynamics of teicoplanin in elderly critically ill patients with pneumonia for optimal dosages. Methods: Fifteen critically ill patients (9 men) ≥ 60 years received teicoplanin 6 mg/kg for three doses followed by standard maintenance doses (6 mg/kg q24h) with renal dosing adjustment. Serial plasma samples from all patients were analyzed simultaneously by population pharmacokinetic modeling using NONMEM. Probability of target attainment (PTA) was calculated through Monte Carlo simulations for various dosing regimens to achieve adequate systemic exposures. Results: The median (interquartile range, IQR) age, body mass index, and creatinine clearance (CrCl) was 75 (64–78) years, 22.5 (20.8–25.4) kg/m2, and 64 (47–106) mL/min, respectively. The median (IQR) peak and trough concentration was 46.5 (42.7–51.0) and 8.7 (7.2–9.5) mg/L. The population pharmacokinetic model showed slower clearance (CL) and larger peripheral volume of distribution (V2) in patients with reduced CrCl: CL (L/h) = 0.629 × (CrCl/64)0.656, V2 (L) = 55.7 × (CrCl/64)-0.665. Model-based simulations showed PTAs ≥85% only for higher-dose regimens (12 mg/kg) up to an MIC of 0.5 mg/L. Conclusions: Standard teicoplanin dosages for pneumonia may provide inadequate systemic exposures in elderly critically ill patients. High-dose regimens should be considered as empiric therapy or for less susceptible pathogens.

Original languageEnglish
Article number154402
JournalJournal of Critical Care
Volume78
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023

Keywords

  • Critical illness
  • Geriatrics
  • Monte Carlo simulation
  • NONMEM
  • Population pharmacokinetics
  • Teicoplanin

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