Linezolid dosage in pediatric patients based on pharmacokinetics and pharmacodynamics

Kazuaki Matsumoto, Akari Shigemi, Ayumi Takeshita, Erika Watanabe, Yuta Yokoyama, Kazuro Ikawa, Norifumi Morikawa, Yasuo Takeda

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Linezolid pharmacokinetic profile in pediatric patients has not been fully characterized, and the dose needed to achieve a pharmacokinetic-pharmacodynamic (PK-PD) target has yet to be established because its efficacy is associated with the area under the plasma drug concentration-time curve (AUC24)/minimum inhibitory concentration (MIC) ratio. The present study aimed to define the pharmacokinetic parameters of intravenous linezolid in pediatric patients and assess the rationale for the approved dosage recommendations. Linezolid was safe, tolerated well, and clinically effective for treating Gram-positive bacteria in five pediatric patients (3-11 years). The mean values for the volume of distribution and total clearance (CL) in a one-compartment model were estimated to be 0.646 ± 0.239 l/kg and 0.171 ± 0.068 l/h/kg, respectively (mean ± S.D.). Based on this analysis, the AUC24 and trough drug concentration in plasma (Cmin) for linezolid doses were predicted to be 175.4 μg h/ml and 3.4 μg/ml for 30 mg/kg/day, 204.7 μg h/ml and 4.3 μg/ml for 35 mg/kg/day, and 263.2 μg h/ml and 6.2 μg/ml for 45 mg/kg/day, respectively. Taking into account that AUC24 should be ≥200 μg h/ml for MIC of 2.0 μg/ml (to achieve an AUC24/MIC ratio of ≥100) and C min should be approximately 7 μg/ml (to avoid thrombocytopenia), we consider the approved dosage of 30 mg/kg/day to be fundamentally rational, but can be underdosed against bacteria with MIC of 2.0 μg/ml; therefore, a dose of 35-45 mg/kg/day is more appropriate to ensure the efficacy and safety of linezolid in pediatric patients.

Original languageEnglish
Pages (from-to)70-73
Number of pages4
JournalJournal of Infection and Chemotherapy
Volume21
Issue number1
DOIs
Publication statusPublished - 2014 May 26
Externally publishedYes

Keywords

  • Daily dose
  • Linezolid
  • Pediatric patient
  • Pharmacokinetics

ASJC Scopus subject areas

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

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