title: A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure.
abstract: OBJECTIVE
  Glucagon-like peptide 2 (GLP-2) analogues are approved for adults with intestinal failure (IF), but no studies have included infants. This study examined the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF.
  
  
  METHODS
  With parental consent (Health Canada Protocol:150,979), parenteral nutrition (PN)-dependent infants were treated with 5-20-μg/kg/day GLP-2 for 3days (phase 1), and if tolerated continued for 42days (phase 2). Nutritional therapy was by primary caregivers, and follow-up was to one year.
  
  
  RESULTS
  Six patients were enrolled, age 5.4±3.2months, bowel length: 27±12% of predicted, PN dependent (67±18% of calories). GLP-2 did not affect vital signs, nor were there significant adverse events during the trial. Dosing 5μg/kg/day gave GLP-2 levels of 52-57pmol/L, with no change in half-life or endogenous GLP-2 levels. Enteral feeds, weight, Z scores, stooling frequency, and citrulline levels improved numerically. The trial was discontinued early because of a drop in potency.
  
  
  CONCLUSIONS
  GLP-2 was well tolerated in infants, and pK was similar to children with no changes in endogenous GLP-2 release. The findings suggest that GLP-2 ligands may be safely used in infants and may have beneficial effects on nutritional status. Further study is required.
  
  
  METHODS
  2b Prospective Interventional Study.
authors.affiliation: Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada. Electronic address: dsigalet@sidra.org.
authors.forename: David L
authors.initials: DL
authors.lastname: Sigalet
authors.affiliation: Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brindle
authors.affiliation: Pediatric Gastroenterology, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
authors.forename: Dana
authors.initials: D
authors.lastname: Boctor
authors.affiliation: Pediatric Surgery, Stollery Children's Hospital/University of Alberta, Edmonton, AB, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Dicken
authors.affiliation: Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
authors.forename: Viona
authors.initials: V
authors.lastname: Lam
authors.affiliation: Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
authors.forename: Lily Sia
authors.initials: LS
authors.lastname: Lu
authors.affiliation: Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: de Heuvel
authors.affiliation: NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D053767:Glucagon-Like Peptide 2 / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D009752:Nutritional Status / Q000187:drug effects; D010288:Parenteral Nutrition; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D053767:Glucagon-Like Peptide 2
keywords: Adaptation; DPP-Iv; Necrotizing enterocolitis; Pharmacokinetics