title: Intestinal fatty-acid binding protein and metronidazole response in premature infants.
abstract: OBJECTIVE
  In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection.
  
  
  METHODS
  We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates.
  
  
  RESULTS
  Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p = 0.006).
  
  
  CONCLUSIONS
  While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants.
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Sampson
authors.affiliation: Wichita Medical Research and Education Foundation, Wichita, KS, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Bloom
authors.affiliation: Children's Hospital-Orange County, Orange, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Arrieta
authors.affiliation: Schools of Medicine and Pharmacy, University of California-San Diego, La Jolla, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Capparelli
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA Department of Pediatrics, Duke University, Durham, NC, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Benjamin
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA Department of Pediatrics, Duke University, Durham, NC, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Smith
authors.affiliation: Division of Pediatric Pharmacology and Therapeutic Innovation, Children's Mercy Hospital, Kansas City, MO, USA Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Kearns
authors.affiliation: Division of Pediatric Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA.
authors.forename: J
authors.initials: J
authors.lastname: van den Anker
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA Department of Pediatrics, Duke University, Durham, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Wolkowiez
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy / Q000652:urine; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000652:urine; D007262:Infusions, Intravenous; D059413:Intraabdominal Infections / Q000188:drug therapy* / Q000652:urine; D016014:Linear Models; D008297:Male; D008795:Metronidazole / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D008795:Metronidazole
keywords: Necrotizing enterocolitis; antimicrobial agents; biomarkers; pharmacokinetics; premature infants