Abstract:
:A population pharmacokinetic (PK) model for meropenem in Japanese pediatric patients with various infectious diseases was developed based on 116 plasma concentrations from 50 pediatric patients. The population PK parameters developed in this analysis are useful for calculation of the percent time above minimum inhibitory concentration (%T>MIC) and for optimal dosing of meropenem in pediatric patients. After dosing at 20 mg/kg t.i.d. by 0.5-h infusion (approved standard dose for pediatric patients in Japan), the target value of 50%T>MIC was achieved, indicating that 20 mg/kg t.i.d. by 0.5-h infusion is effective for susceptible bacteria. In contrast, for bacteria with higher MICs such as Pseudomonas aeruginosa (MIC ≥ 2 µg/mL), the probability of target attainment of 50%T>MIC was 60.7% at a dose of 40 mg/kg t.i.d. by 0.5-h infusion (highest dose approved for pediatric patients in Japan). The simulations described in this article indicated that 40 mg/kg t.i.d. with a longer infusion duration (e.g., 4 h) is more effective against bacteria with a MIC higher than 2 µg/mL. The predicted probability of target attainment for 50%T>MIC (97.0%) was well correlated not only to the microbiological efficacy rate (97.0%) but also to the clinical efficacy rate (95.9%) in the present phase 3 study.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Ohata Y,Tomita Y,Nakayama M,Kozuki T,Sunakawa K,Tanigawara Ydoi
10.2133/dmpk.dmpk-11-rg-027subject
Has Abstractpub_date
2011-01-01 00:00:00pages
523-31issue
5eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/DMPK-11-RG-027journal_volume
26pub_type
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