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

研究成果: Article査読

6 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)69-77
ページ数9
ジャーナルJapanese Journal of Chemotherapy
58
SUPPL. 2
出版ステータスPublished - 2010 10 1

ASJC Scopus subject areas

  • 薬理学
  • 薬理学(医学)

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