Population pharmacokinetics and pharmacodynamics of tosufloxacin granules in pediatric infectious diseases

Keisuke Sunakawa, Naoichi Iwai, Satoshi Iwata, Kazunobu Ouchi, Hiroshi Sakata, Kenji Suzuki, Yukiko Iino, Hidenobu Taiji, Fumiyo Kudo, Kenji Nozawa

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The population pharmacokinetics and pharmacodynamics(PK-PD) of 10% tosufloxacin granules(TFLX) were performed in pediatric infectious diseases in Japanese. Infants and children aged (1-15 years old) with bacterial pneumonia or acute otitis media were orally administered a dose of either 4 mg/kg TFLX (not exceeding 120 mg per dose) or 6 mg/kg TFLX (not exceeding 180 mg per dose) twice daily, and 416 plasma concentrations were measured from 222 pediatric subjects were obtained. Population pharmacokinetic parameters were estimated using a nonlinear mixed effect model(NONMEM), applying a one-compartment model with first-order absorption as a pharmacokinetic model. Covariates were tested for their potential influence on TFLX pharmacokinetics. Significant influence of body weight was found in oral clearance(CL/F) and volume of distribution(Vd/F). Plasma TFLX concentrations versus a time profile of 4 mg/kg TFLX in pediatric subjects were similar to those between 200 mg TFLX and 100 mg TFLX in adults. Pharmacokinetic parameters of 4 mg/kg TFLX in pediatric subjects were similar to those of 200 mg TFLX in adults. The attaining probability of target unbound fractions of AUC/MIC(fAUC/MIC) in those administered 4 or 6 mg/kg TFLX was calculated by Monte Carlo simulation. A twice-daily oral dose of 4 mg/kg TFLX is expected to show superior clinical efficacy against Streptococcus pneumoniae, Moraxella(Branhamella) catarrhalis, and Haemophilus influenzae. These results indicate that 4.1 mg/kg TFLX (OZEX® 15% granules, 6 mg/kg tosufloxacin tosilate hydrate) twice daily is effective.

Original languageEnglish
Pages (from-to)69-77
Number of pages9
JournalJapanese Journal of Chemotherapy
Volume58
Issue numberSUPPL. 2
Publication statusPublished - 2010 Oct 1

Keywords

  • Child
  • Dose finding
  • PK-PD
  • Population pharmacokinetics
  • Tosufloxacin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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