title: Population pharmacokinetic-pharmacodynamic target attainment analysis of imipenem plasma and urine data in neonates and children.
abstract: BACKGROUND
  Population pharmacokinetic (PK)-pharmacodynamic target attainment analysis of imipenem was performed to elucidate the PK properties in neonates and children and to rationalize and optimize dosing regimens.
  
  
  METHODS
  Population PK models were separately developed in neonates and children by simultaneously fitting plasma and urine data from 60 neonates and 39 children. The newly developed models were then used to estimate the probability of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration) against clinical isolates of common bacteria in pediatric patients.
  
  
  RESULTS
  The data were best described by a 1-compartment model in neonates and a 2-compartment model in children, respectively. Renal clearance in children (0.187 L/h/kg) was double that of neonates (0.0783 L/h/kg), whereas the volume of distribution at steady-state was approximately 1.8-fold larger in neonates (0.466 L/kg) than in children (0.260 L/kg). Age was not a statistically significant covariate in the PK of both groups. Infusions (0.5 h) of 15 mg/kg every 8 h (45 mg/kg/day) and 25 mg/kg every 12 h (50 mg/kg/day) were shown to be sufficient against common bacterial isolates in both patient populations. However, 1.5-h infusions of 25 mg/kg every 8 h (75 mg/kg/day) in neonates and 25 mg/kg every 6 h (100 mg/kg/day) in children were required to be effective against Pseudomonas aeruginosa (minimum inhibitory concentration for 90% of the isolates=16 μg/mL).
  
  
  CONCLUSIONS
  These results explain the changes in imipenem PK properties during the human growth process and provide guidance for tailoring dosing regimens in each pediatric age group.
authors.affiliation: From the *Department of Clinical Pharmacotherapy, Hiroshima University; and †Department of Infectious Diseases, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohge
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001424:Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008954:Models, Biological
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem