A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure
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A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure. / Sigalet, David L; Brindle, Mary E; Boctor, Dana; Dicken, Bryan; Lam, Viona; Lu, Lily Sia; de Heuvel, Elaine; Hartmann, Bolette; Holst, Jens J.
I: Journal of Pediatric Surgery, Bind 52, Nr. 5, 29.01.2017, s. 749-754.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure
AU - Sigalet, David L
AU - Brindle, Mary E
AU - Boctor, Dana
AU - Dicken, Bryan
AU - Lam, Viona
AU - Lu, Lily Sia
AU - de Heuvel, Elaine
AU - Hartmann, Bolette
AU - Holst, Jens J
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2017/1/29
Y1 - 2017/1/29
N2 - BACKGROUND & AIMS: 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.LEVEL OF EVIDENCE: 2b Prospective Interventional Study.
AB - BACKGROUND & AIMS: 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.LEVEL OF EVIDENCE: 2b Prospective Interventional Study.
KW - Journal Article
U2 - 10.1016/j.jpedsurg.2017.01.034
DO - 10.1016/j.jpedsurg.2017.01.034
M3 - Journal article
C2 - 28209419
VL - 52
SP - 749
EP - 754
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
SN - 0022-3468
IS - 5
ER -
ID: 174400645