Evaluation of usefulness and PK-PD analysis of meropenem in children with various infections

Yoshitake Sato, Mitsuru Sandoh, Hideaki Hanaki, Yumiko Suzuki, Mikinobu Yoshida, Junko Kizu

Research output: Contribution to journalArticle

Abstract

We conducted a study of meropenem(MEPM) in a total of 29 children with various infections (moderate to severe pneumonia in 25, upper respiratory infection in 3, and urinary tract infection in 1) to demonstrate the efficacy and safety and assess the relationship between the time above the minimal inhibitory concentration (MIC) (T > MIC), calculated based on the pharmacokinetic simulation analysis using blood concentration data from subjects, and the clinical response. In accordance with the package insert in Japan, MEPM was administered at a dose of 20 mg/kg three times daily, the highest dose in the usual dosage range. Each dose was administered by infusion over 30 minutes. The minimum inhibitory concentration (MIC) values of MEPM were less than 0.5 μg/mL for all 26 strains isolated from the patients, showing that these causative bacteria were highly susceptible to the drug. The clinical response was judged to be excellent in all patients treated with MEPM, irrespective of the target disease, severity, or presence or absence of previous antimicrobial therapy. No drug-related or -unrelated adverse event was reported during or after MEPM therapy. In general, the observed serum concentrations of MEPM were within the 95% prediction interval based on the population pharmacokinetic(PPK) model established using data from clinical trials, showing a good correlation. On the basis of the simulation of blood concentrations in individual subjects determined using Bayesian estimation, T > MIC of MEPM was calculated from the MIC values for the 26 isolates in the present study. For all strains, the T > MIC was higher than 40%, an amount that is associated with the maximal bactericidal activity of carbapenems. Supporting a previous report on the efficacy of MEPM based on a pharmacokinetics-pharmacodynamics(PK- PD) simulation analysis, the current study showed that the T > MIC of MEPM may serve as a predictor of the clinical response.

Original languageEnglish
Pages (from-to)335-341
Number of pages7
JournalJapanese Journal of Chemotherapy
Volume60
Issue number3
Publication statusPublished - 2012 May 1

Keywords

  • Child
  • Clinical effect
  • Meropenem
  • PK-PD
  • Time above MIC

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Sato, Y., Sandoh, M., Hanaki, H., Suzuki, Y., Yoshida, M., & Kizu, J. (2012). Evaluation of usefulness and PK-PD analysis of meropenem in children with various infections. Japanese Journal of Chemotherapy, 60(3), 335-341.