Intestinal fatty-acid binding protein and metronidazole response in premature infants

Article type: Research Article

Authors: Sampson, M.R.^; | Bloom, B.T. | Arrieta, A. | Capparelli, E. | Benjamin Jr., D.K.^; | Smith, P.B.^; | Kearns, G.L.^; | van den Anker, J. | Cohen-Wolkowiez, M.^; | Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee

Affiliations: Duke Clinical Research Institute, Durham, NC, USA | UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA | Wichita Medical Research and Education Foundation, Wichita, KS, USA | Children's Hospital–Orange County, Orange, CA, USA | Schools of Medicine and Pharmacy, University of California–San Diego, La Jolla, CA, USA | Department of Pediatrics, Duke University, Durham, NC, USA | 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 | Division of Pediatric Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA

Note: [] Corresponding author: Dr. Michael Cohen-Wolkowiez, Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705, USA. Tel.: +1 919 668 8812; Fax: +1 919 668 7058; E-mail: michael.cohenwolkowiez@duke.edu

Abstract: OBJECTIVES: 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. STUDY DESIGN: 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). CONCLUSION: 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.

Keywords: Necrotizing enterocolitis, biomarkers, pharmacokinetics, premature infants, antimicrobial agents

DOI: 10.3233/NPM-1477013

Journal: Journal of Neonatal-Perinatal Medicine, vol. 7, no. 3, pp. 223-228, 2014