title: Pharmacokinetics and pharmacodynamics of meropenem in children with severe infection.
abstract: This study aimed to describe the pharmacokinetic (PK) characteristics of meropenem in children with severe infections and to assess the pharmacokinetic/pharmacodynamic (PK/PD) profiles of various meropenem dosage regimens in these patients. Fourteen children with severe infections received intravenous (i.v.) bolus doses of meropenem (20 mg/kg/dose) every 8 h (q8h). Serum samples were obtained before and serially after the second dose of meropenem, and a population PK analysis was performed. The final model was used to simulate serum concentration-time profiles with various dosage regimens. The PK/PD target was to achieve a serum meropenem concentration higher than the minimum inhibitory concentration (MIC) of the causative organism (i.e. Pseudomonas aeruginosa and Enterobacteriaceae) for ≥40% of the dosing interval (40%T>MIC). The median age and weight of the children were 6.0 years and 20.0 kg, respectively. Meropenem serum concentration-time profiles were best described by a two-compartmental model with first-order elimination. The simulations showed that the probabilities of target attainment (PTAs) for organisms with an MIC of 1 mg/L were 0.678 and 1.000 following i.v. bolus and 3-h infusion of meropenem (20 mg/kg/dose), respectively. Using a 3-h infusion of a 20 mg/kg/dose, the PTA was 0.999 and 0.765 for organisms with MICs of 4 mg/L and 8 mg/L, respectively. Meropenem given as i.v. bolus doses of 20 mg/kg/dose q8h appeared to be inadequate for PK/PD target attainment for organisms with an MIC of 1 mg/L. The simulations showed that meropenem administration via a 3-h infusion using the same dose improved the PTA.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Kritsana
authors.initials: K
authors.lastname: Kongthavonsakul
authors.affiliation: Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Aroonrut
authors.initials: A
authors.lastname: Lucksiri
authors.affiliation: Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Suntara
authors.initials: S
authors.lastname: Eakanunkul
authors.affiliation: Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Somjing
authors.initials: S
authors.lastname: Roongjang
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Satja
authors.initials: S
authors.lastname: Issaranggoon Na Ayuthaya
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: oberdorferp@gmail.com.
authors.forename: Peninnah
authors.initials: P
authors.lastname: Oberdorfer
mesh_terms: D061605:Administration, Intravenous; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D016638:Critical Illness; D004755:Enterobacteriaceae / Q000187:drug effects; D004756:Enterobacteriaceae Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D044967:Serum / Q000737:chemistry; D013845:Thienamycins / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: Children; Meropenem; Pharmacodynamics; Pharmacokinetics; Severe infection