title: Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure.
abstract: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure.
  
  
  
  Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year.
  
  
  
  Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in z scores and citrulline levels; the z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued.
  
  
  
  GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.
authors.affiliation: 1 Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: David L
authors.initials: DL
authors.lastname: Sigalet
authors.affiliation: 1 Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Brindle
authors.affiliation: 2 Pediatric Gastroenterology, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Dana
authors.initials: D
authors.lastname: Boctor
authors.affiliation: 3 Surgery (Pediatric), Stollery Children's Hospital/University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Casey
authors.affiliation: 3 Surgery (Pediatric), Stollery Children's Hospital/University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Dicken
authors.affiliation: 4 Pediatric Surgery, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Butterworth
authors.affiliation: 1 Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Viona
authors.initials: V
authors.lastname: Lam
authors.affiliation: 1 Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Vikram
authors.initials: V
authors.lastname: Karnik
authors.affiliation: 1 Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: de Heuvel
authors.affiliation: 5 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: 5 NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Holst
mesh_terms: D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004750:Enteral Nutrition; D005500:Follow-Up Studies; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D010288:Parenteral Nutrition; D018401:Sample Size; D012778:Short Bowel Syndrome / Q000097:blood / Q000628:therapy*
chemical_list: D053767:Glucagon-Like Peptide 2
keywords: adaptation; dipeptidyl peptidase IV; necrotizing enterocolitis; pharmacokinetics