Population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome

Abstract Teduglutide is a recombinant analog of human glucagon‐like peptide‐2 that regulates the functional and structural integrity of the cells lining the gastrointestinal tract. Teduglutide is approved for the treatment of patients with short bowel syndrome (SBS) who are dependent on parenteral s...

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Autores principales:	Jean‐Francois Marier, Claudia Jomphe, Thomas Peyret, Yi Wang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/e1ad778fc0454aba88a07040677a1f2e
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spelling	oai:doaj.org-article:e1ad778fc0454aba88a07040677a1f2e2021-11-19T17:51:35ZPopulation pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome1752-80621752-805410.1111/cts.13117https://doaj.org/article/e1ad778fc0454aba88a07040677a1f2e2021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13117https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract Teduglutide is a recombinant analog of human glucagon‐like peptide‐2 that regulates the functional and structural integrity of the cells lining the gastrointestinal tract. Teduglutide is approved for the treatment of patients with short bowel syndrome (SBS) who are dependent on parenteral support (PS). Population pharmacokinetic (PK) and exposure‐response analyses were performed to support teduglutide dosing in patients with SBS. The analysis included 219 patients with SBS (aged <1 year, 5 patients; 1–11 years, 86 patients; 12–17 years, 8 patients; 18–79 years, 120 patients), and 259 non‐SBS subjects (including healthy volunteers and subjects with renal or liver impairment). A one‐compartment model with first‐order absorption and linear elimination adequately characterized the PKs of teduglutide. In patients with SBS, the apparent clearance (CL/F), volume of distribution (V/F), and elimination half‐life of teduglutide were 16.0 L/h, 33.9 L, and 1.47 h, respectively. CL/F depended on body weight and renal function, and V/F depended on body weight and age. Maximum concentration (Cmax) of teduglutide was similar in adult and pediatric patients, and in Japanese and non‐Japanese patients. A time‐ and exposure‐response model dependent on the Cmax of teduglutide adequately characterized the reduction in PS over more than 2 years of treatment. Daily dosing of 0.05 mg/kg teduglutide resulted in a maximum reduction in PS of 5.76 L/week. Higher Cmax values were associated with a more important reduction in PS over time. Adult and pediatric patients with SBS presented similar PKs and response to teduglutide.Jean‐Francois MarierClaudia JompheThomas PeyretYi WangWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2497-2509 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
spellingShingle	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270 Jean‐Francois Marier Claudia Jomphe Thomas Peyret Yi Wang Population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome
description	Abstract Teduglutide is a recombinant analog of human glucagon‐like peptide‐2 that regulates the functional and structural integrity of the cells lining the gastrointestinal tract. Teduglutide is approved for the treatment of patients with short bowel syndrome (SBS) who are dependent on parenteral support (PS). Population pharmacokinetic (PK) and exposure‐response analyses were performed to support teduglutide dosing in patients with SBS. The analysis included 219 patients with SBS (aged <1 year, 5 patients; 1–11 years, 86 patients; 12–17 years, 8 patients; 18–79 years, 120 patients), and 259 non‐SBS subjects (including healthy volunteers and subjects with renal or liver impairment). A one‐compartment model with first‐order absorption and linear elimination adequately characterized the PKs of teduglutide. In patients with SBS, the apparent clearance (CL/F), volume of distribution (V/F), and elimination half‐life of teduglutide were 16.0 L/h, 33.9 L, and 1.47 h, respectively. CL/F depended on body weight and renal function, and V/F depended on body weight and age. Maximum concentration (Cmax) of teduglutide was similar in adult and pediatric patients, and in Japanese and non‐Japanese patients. A time‐ and exposure‐response model dependent on the Cmax of teduglutide adequately characterized the reduction in PS over more than 2 years of treatment. Daily dosing of 0.05 mg/kg teduglutide resulted in a maximum reduction in PS of 5.76 L/week. Higher Cmax values were associated with a more important reduction in PS over time. Adult and pediatric patients with SBS presented similar PKs and response to teduglutide.
format	article
author	Jean‐Francois Marier Claudia Jomphe Thomas Peyret Yi Wang
author_facet	Jean‐Francois Marier Claudia Jomphe Thomas Peyret Yi Wang
author_sort	Jean‐Francois Marier
title	Population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome
title_short	Population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome
title_full	Population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome
title_fullStr	Population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome
title_full_unstemmed	Population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome
title_sort	population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e1ad778fc0454aba88a07040677a1f2e
work_keys_str_mv	AT jeanfrancoismarier populationpharmacokineticsandexposureresponseanalysesofteduglutideinadultandpediatricpatientswithshortbowelsyndrome AT claudiajomphe populationpharmacokineticsandexposureresponseanalysesofteduglutideinadultandpediatricpatientswithshortbowelsyndrome AT thomaspeyret populationpharmacokineticsandexposureresponseanalysesofteduglutideinadultandpediatricpatientswithshortbowelsyndrome AT yiwang populationpharmacokineticsandexposureresponseanalysesofteduglutideinadultandpediatricpatientswithshortbowelsyndrome
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Population pharmacokinetics and exposure‐response analyses of teduglutide in adult and pediatric patients with short bowel syndrome

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