Pharmacokinetics, toxicity and clinical efficacy of linezolid in Japanese pediatric patients

Chika Ogami, Yasuhiro Tsuji*, Hideto To, Yoshihiro Yamamoto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Objectives: The aims of the present study were (a) to evaluate the pharmacokinetics of linezolid, and (b) to assess the toxicity and clinical efficacy of linezolid in Japanese pediatric patients. Patients and methods: Routine clinical data including serum linezolid total and unbound concentrations were collected from 15 pediatric patients (0–13 years old). Pharmacokinetics of linezolid was assumed to follow one-compartment with the first-order absorption model. The relationship between risk for thrombocytopenia and linezolid concentrations, and the variations in C-reactive protein (CRP) concentrations and body temperatures were evaluated as clinical efficacy assessment. Results: Body weight (WT) and maturation of body function were significant covariates for pharmacokinetics of linezolid in pediatric patients. The elimination half-life of linezolid in a pediatric patient with a WT of 9.9 kg and age of 24 months (median of this study) was 3.0 h. Thrombocytopenia was detected in three patients (21.4%), and the minimum concentrations (Cmin) in these patients were significantly higher than those in patients without thrombocytopenia (P < 0.05). The CRP concentrations decreased more than 50% in all pediatric patients after the treatment with linezolid, however body temperatures at the end of treatment were higher than 37.5 °C in 6 patients (42.9%). Conclusions: Although dose adjustment based on body size was performed for pediatric patients, thrombocytopenia was detected in 21.4% of pediatric patients, and higher Cmin was associated with the risk of thrombocytopenia. These results encourage the implementation of individual dose adjustment based on linezolid serum concentrations for safe and appropriate treatment with linezolid.

Original languageEnglish
Pages (from-to)979-986
Number of pages8
JournalJournal of Infection and Chemotherapy
Volume25
Issue number12
DOIs
StatePublished - 2019/12

Keywords

  • Children
  • Efficacy
  • Linezolid
  • Pharmacokinetics
  • Toxicity

ASJC Scopus subject areas

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

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