Population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia

Abstract A subcutaneous formulation of the anti‐CD20 antibody rituximab has been developed. Fixed‐dose subcutaneous rituximab delivers noninferior serum trough concentrations (Ctrough), ensuring similar target saturation and comparable efficacy/safety, to intravenous rituximab, but with simplified a...

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Autores principales:	Ekaterina Gibiansky, Leonid Gibiansky, Clarisse Chavanne, Nicolas Frey, Candice Jamois
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/96de8a1a1020405cb52160c9fa76dd90
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spelling	oai:doaj.org-article:96de8a1a1020405cb52160c9fa76dd902021-11-19T15:35:29ZPopulation pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia2163-830610.1002/psp4.12665https://doaj.org/article/96de8a1a1020405cb52160c9fa76dd902021-08-01T00:00:00Zhttps://doi.org/10.1002/psp4.12665https://doaj.org/toc/2163-8306Abstract A subcutaneous formulation of the anti‐CD20 antibody rituximab has been developed. Fixed‐dose subcutaneous rituximab delivers noninferior serum trough concentrations (Ctrough), ensuring similar target saturation and comparable efficacy/safety, to intravenous rituximab, but with simplified and shortened preparation and administration. We aimed to characterize the pharmacokinetic (PK) and exposure–response properties of subcutaneous rituximab. Data from two clinical trials were analyzed to describe PKs and pharmacodynamics in patients with chronic lymphocytic leukemia following intravenous and subcutaneous rituximab administration. Intravenous and subcutaneous rituximab were described by a linear two‐compartment population PK model with time‐dependent and time‐independent clearances, and first‐order subcutaneous absorption. Main covariates influencing exposure were body size and baseline white blood cell count. Occurrence of adverse events was not correlated with rituximab exposure. Although greater and more sustainable B‐cell depletion was observed with higher exposure, inherent limitations to the data (use of one dose level, and time‐dependent and target‐impacted PKs) prevented reliable assessment of exposure–response relationships.Ekaterina GibianskyLeonid GibianskyClarisse ChavanneNicolas FreyCandice JamoisWileyarticleTherapeutics. PharmacologyRM1-950ENCPT: Pharmacometrics & Systems Pharmacology, Vol 10, Iss 8, Pp 914-927 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Ekaterina Gibiansky Leonid Gibiansky Clarisse Chavanne Nicolas Frey Candice Jamois Population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia
description	Abstract A subcutaneous formulation of the anti‐CD20 antibody rituximab has been developed. Fixed‐dose subcutaneous rituximab delivers noninferior serum trough concentrations (Ctrough), ensuring similar target saturation and comparable efficacy/safety, to intravenous rituximab, but with simplified and shortened preparation and administration. We aimed to characterize the pharmacokinetic (PK) and exposure–response properties of subcutaneous rituximab. Data from two clinical trials were analyzed to describe PKs and pharmacodynamics in patients with chronic lymphocytic leukemia following intravenous and subcutaneous rituximab administration. Intravenous and subcutaneous rituximab were described by a linear two‐compartment population PK model with time‐dependent and time‐independent clearances, and first‐order subcutaneous absorption. Main covariates influencing exposure were body size and baseline white blood cell count. Occurrence of adverse events was not correlated with rituximab exposure. Although greater and more sustainable B‐cell depletion was observed with higher exposure, inherent limitations to the data (use of one dose level, and time‐dependent and target‐impacted PKs) prevented reliable assessment of exposure–response relationships.
format	article
author	Ekaterina Gibiansky Leonid Gibiansky Clarisse Chavanne Nicolas Frey Candice Jamois
author_facet	Ekaterina Gibiansky Leonid Gibiansky Clarisse Chavanne Nicolas Frey Candice Jamois
author_sort	Ekaterina Gibiansky
title	Population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia
title_short	Population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia
title_full	Population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia
title_fullStr	Population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia
title_full_unstemmed	Population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia
title_sort	population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/96de8a1a1020405cb52160c9fa76dd90
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Population pharmacokinetic and exposure–response analyses of intravenous and subcutaneous rituximab in patients with chronic lymphocytic leukemia

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