title: Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections.
abstract: BACKGROUND
  Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events.
  
  
  METHODS
  Premature and term infants <91 days old hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20 to 30 mg/kg of body weight every 8 to 12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM.
  
  
  RESULTS
  In this study, 200 infants were enrolled and received the study drug. Of them, 188 infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23-40) weeks and 21 (1-92) days, respectively. In the final PK model, meropenem clearance was strongly associated with serum creatinine and postmenstrual age (clearance [L/h/kg] = 0.12*[(0.5/serum creatinine)**0.27]*[(postmenstrual age/32.7)**1.46]). Meropenem concentrations remained >4 μg/mL for 50% of the dose interval and >2 μg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5-148).
  
  
  CONCLUSIONS
  Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.
authors.affiliation: Department of Pediatrics, Duke University, Durham, NC, USA.
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen-Wolkowiez
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Castro
authors.forename: Brenda
authors.initials: B
authors.lastname: Poindexter
authors.forename: Margarita
authors.initials: M
authors.lastname: Bidegain
authors.forename: Joern-Hendrik
authors.initials: JH
authors.lastname: Weitkamp
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schelonka
authors.forename: Robert M
authors.initials: RM
authors.lastname: Ward
authors.forename: Kelly
authors.initials: K
authors.lastname: Wade
authors.forename: Gloria
authors.initials: G
authors.lastname: Valencia
authors.forename: David
authors.initials: D
authors.lastname: Burchfield
authors.forename: Antonio
authors.initials: A
authors.lastname: Arrieta
authors.forename: Varsha
authors.initials: V
authors.lastname: Bhatt-Mehta
authors.forename: Michele
authors.initials: M
authors.lastname: Walsh
authors.forename: Anand
authors.initials: A
authors.lastname: Kantak
authors.forename: Maynard
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Janice E
authors.initials: JE
authors.lastname: Sullivan
authors.forename: Neil
authors.initials: N
authors.lastname: Finer
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Brozanski
authors.forename: Pablo
authors.initials: P
authors.lastname: Sanchez
authors.forename: John
authors.initials: J
authors.lastname: van den Anker
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Blumer
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kearns
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
authors.forename: Ravinder
authors.initials: R
authors.lastname: Anand
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D059413:Intraabdominal Infections / Q000188:drug therapy*; D000077731:Meropenem; D010949:Plasma / Q000737:chemistry*; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem