title: Optimal dosage regimen of meropenem for pediatric patients based on pharmacokinetic/pharmacodynamic considerations.
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.
authors: Drug Development Division, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan.
authors: Yuka
authors: Y
authors: Ohata
authors: Yoshiko
authors: Y
authors: Tomita
authors: Mitsunobu
authors: M
authors: Nakayama
authors: Tsuneo
authors: T
authors: Kozuki
authors: Keisuke
authors: K
authors: Sunakawa
authors: Yusuke
authors: Y
authors: Tanigawara
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007564:Japan; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem