Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma

Abstract A population pharmacokinetic model was developed using data from healthy subjects and patients with moderate‐to‐severe asthma receiving intravenous or subcutaneous dupilumab doses. A total of nine phase I to phase III studies were pooled (202 healthy subjects and 1912 patients with asthma i...

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Autores principales:	Li Zhang, Yue Gao, Meng Li, Christine Xu, John D. Davis, Vanaja Kanamaluru, Qiang Lu
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/084f8b44c1734d9c9e6070fdd4e90523
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spelling	oai:doaj.org-article:084f8b44c1734d9c9e6070fdd4e905232021-11-19T15:35:29ZPopulation pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma2163-830610.1002/psp4.12667https://doaj.org/article/084f8b44c1734d9c9e6070fdd4e905232021-08-01T00:00:00Zhttps://doi.org/10.1002/psp4.12667https://doaj.org/toc/2163-8306Abstract A population pharmacokinetic model was developed using data from healthy subjects and patients with moderate‐to‐severe asthma receiving intravenous or subcutaneous dupilumab doses. A total of nine phase I to phase III studies were pooled (202 healthy subjects and 1912 patients with asthma including 68 adolescents) in the model development. The best model was a two‐compartment model with parallel linear and nonlinear Michaelis–Menten elimination with first order absorption. The PK parameter estimates were distribution volume of central compartment 2.76 L, linear elimination rate 0.0418 1/day, and subcutaneous bioavailability 60.9%. Pharmacokinetics (PK) properties of dupilumab in patients with asthma were determined to be comparable to those of healthy subjects and patients with atopic dermatitis. Only body weight exerts a notable effect explaining between‐subject variability in dupilumab PK, but dose adjustment for weight is not warranted based on results from clinical studies. There is no PK difference between adolescent and adult patients with asthma after correction for body weight.Li ZhangYue GaoMeng LiChristine XuJohn D. DavisVanaja KanamaluruQiang LuWileyarticleTherapeutics. PharmacologyRM1-950ENCPT: Pharmacometrics & Systems Pharmacology, Vol 10, Iss 8, Pp 941-952 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Li Zhang Yue Gao Meng Li Christine Xu John D. Davis Vanaja Kanamaluru Qiang Lu Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma
description	Abstract A population pharmacokinetic model was developed using data from healthy subjects and patients with moderate‐to‐severe asthma receiving intravenous or subcutaneous dupilumab doses. A total of nine phase I to phase III studies were pooled (202 healthy subjects and 1912 patients with asthma including 68 adolescents) in the model development. The best model was a two‐compartment model with parallel linear and nonlinear Michaelis–Menten elimination with first order absorption. The PK parameter estimates were distribution volume of central compartment 2.76 L, linear elimination rate 0.0418 1/day, and subcutaneous bioavailability 60.9%. Pharmacokinetics (PK) properties of dupilumab in patients with asthma were determined to be comparable to those of healthy subjects and patients with atopic dermatitis. Only body weight exerts a notable effect explaining between‐subject variability in dupilumab PK, but dose adjustment for weight is not warranted based on results from clinical studies. There is no PK difference between adolescent and adult patients with asthma after correction for body weight.
format	article
author	Li Zhang Yue Gao Meng Li Christine Xu John D. Davis Vanaja Kanamaluru Qiang Lu
author_facet	Li Zhang Yue Gao Meng Li Christine Xu John D. Davis Vanaja Kanamaluru Qiang Lu
author_sort	Li Zhang
title	Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma
title_short	Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma
title_full	Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma
title_fullStr	Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma
title_full_unstemmed	Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma
title_sort	population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/084f8b44c1734d9c9e6070fdd4e90523
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Population pharmacokinetic analysis of dupilumab in adult and adolescent patients with asthma

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