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.

In: Journal of Pediatric Surgery, Vol. 52, No. 5, 29.01.2017, p. 749-754.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Sigalet, DL, Brindle, ME, Boctor, D, Dicken, B, Lam, V, Lu, LS, de Heuvel, E, Hartmann, B & Holst, JJ 2017, 'A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure', Journal of Pediatric Surgery, vol. 52, no. 5, pp. 749-754. https://doi.org/10.1016/j.jpedsurg.2017.01.034

APA

Sigalet, D. L., Brindle, M. E., Boctor, D., Dicken, B., Lam, V., Lu, L. S., ... Holst, J. J. (2017). A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure. Journal of Pediatric Surgery, 52(5), 749-754. https://doi.org/10.1016/j.jpedsurg.2017.01.034

Vancouver

Sigalet DL, Brindle ME, Boctor D, Dicken B, Lam V, Lu LS et al. A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure. Journal of Pediatric Surgery. 2017 Jan 29;52(5):749-754. https://doi.org/10.1016/j.jpedsurg.2017.01.034

Author

Sigalet, David L ; Brindle, Mary E ; Boctor, Dana ; Dicken, Bryan ; Lam, Viona ; Lu, Lily Sia ; de Heuvel, Elaine ; Hartmann, Bolette ; Holst, Jens J. / A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure. In: Journal of Pediatric Surgery. 2017 ; Vol. 52, No. 5. pp. 749-754.

Bibtex

@article{b63e8f93f3f84fcc8b6dd1c32e209ebd,
title = "A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure",
abstract = "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.",
keywords = "Journal Article",
author = "Sigalet, {David L} and Brindle, {Mary E} and Dana Boctor and Bryan Dicken and Viona Lam and Lu, {Lily Sia} and {de Heuvel}, Elaine and Bolette Hartmann and Holst, {Jens J}",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2017",
month = "1",
day = "29",
doi = "10.1016/j.jpedsurg.2017.01.034",
language = "English",
volume = "52",
pages = "749--754",
journal = "Journal of Pediatric Surgery",
issn = "0022-3468",
publisher = "W.B.Saunders Co.",
number = "5",

}

RIS

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