Population Pharmacokinetics of CC-122

Yiming Cheng,1 Jian Chen,2 Michael Pourdehnad,3 Simon Zhou,1 Yan Li1 1Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Summit, NJ, USA; 2Non-Clinical Research & Development, Bristol Myers Squibb, Summit, NJ, USA; 3Early Clinical Development, Bristol Myers Squibb, San Fr...

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Autores principales:	Cheng Y, Chen J, Pourdehnad M, Zhou S, Li Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	cc-122 population pharmacokinetics renal impairment Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/057f02a8d2314ce997e30bc610a5447f
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spelling	oai:doaj.org-article:057f02a8d2314ce997e30bc610a5447f2021-12-02T14:51:56ZPopulation Pharmacokinetics of CC-1221179-1438https://doaj.org/article/057f02a8d2314ce997e30bc610a5447f2021-04-01T00:00:00Zhttps://www.dovepress.com/population-pharmacokinetics-of-cc-122-peer-reviewed-fulltext-article-CPAAhttps://doaj.org/toc/1179-1438Yiming Cheng,1 Jian Chen,2 Michael Pourdehnad,3 Simon Zhou,1 Yan Li1 1Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Summit, NJ, USA; 2Non-Clinical Research & Development, Bristol Myers Squibb, Summit, NJ, USA; 3Early Clinical Development, Bristol Myers Squibb, San Francisco, CA, USACorrespondence: Yan LiClinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, 556 Morris Ave, Summit, NJ, 07901, USATel +1 908-481-6203Email yan.li@bms.comBackground: CC-122 is a cereblon-modulating agent that exerts direct cell-autonomous activity against malignant B cells and immunomodulatory effects. Herein, a population pharmacokinetic (popPK) model of CC-122 was developed and the influence of demographic and disease-related covariates on population pharmacokinetic parameters was assessed based on data from three clinical studies of CC-122 (dose range, 0.5– 15 mg) in healthy subjects and cancer patients.Methods: Nonlinear mixed effects modeling was employed in developing a population pharmacokinetic model of CC-122 based on 298 patients from 3 clinical studies.Results: The PK of CC-122 was adequately described with a two-compartment model with first-order absorption and elimination. Tumor types were found to be significantly correlated with apparent clearance (CL/F) and apparent volume of distribution of the central compartment. Creatinine clearance was identified as a statistically significant covariate of CL/F. Sex and body weight were statistically but not clinically relevant on V2/F.Conclusion: In conclusion, the two-compartment model built can be used to adequately describe the time course of the population pharmacokinetics of CC-122 and should serve as the basis for dose adjustment decision-making of CC-122.Keywords: CC-122, population pharmacokinetics, renal impairmentCheng YChen JPourdehnad MZhou SLi YDove Medical Pressarticlecc-122population pharmacokineticsrenal impairmentTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 13, Pp 61-71 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cc-122 population pharmacokinetics renal impairment Therapeutics. Pharmacology RM1-950
spellingShingle	cc-122 population pharmacokinetics renal impairment Therapeutics. Pharmacology RM1-950 Cheng Y Chen J Pourdehnad M Zhou S Li Y Population Pharmacokinetics of CC-122
description	Yiming Cheng,1 Jian Chen,2 Michael Pourdehnad,3 Simon Zhou,1 Yan Li1 1Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Summit, NJ, USA; 2Non-Clinical Research & Development, Bristol Myers Squibb, Summit, NJ, USA; 3Early Clinical Development, Bristol Myers Squibb, San Francisco, CA, USACorrespondence: Yan LiClinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, 556 Morris Ave, Summit, NJ, 07901, USATel +1 908-481-6203Email yan.li@bms.comBackground: CC-122 is a cereblon-modulating agent that exerts direct cell-autonomous activity against malignant B cells and immunomodulatory effects. Herein, a population pharmacokinetic (popPK) model of CC-122 was developed and the influence of demographic and disease-related covariates on population pharmacokinetic parameters was assessed based on data from three clinical studies of CC-122 (dose range, 0.5– 15 mg) in healthy subjects and cancer patients.Methods: Nonlinear mixed effects modeling was employed in developing a population pharmacokinetic model of CC-122 based on 298 patients from 3 clinical studies.Results: The PK of CC-122 was adequately described with a two-compartment model with first-order absorption and elimination. Tumor types were found to be significantly correlated with apparent clearance (CL/F) and apparent volume of distribution of the central compartment. Creatinine clearance was identified as a statistically significant covariate of CL/F. Sex and body weight were statistically but not clinically relevant on V2/F.Conclusion: In conclusion, the two-compartment model built can be used to adequately describe the time course of the population pharmacokinetics of CC-122 and should serve as the basis for dose adjustment decision-making of CC-122.Keywords: CC-122, population pharmacokinetics, renal impairment
format	article
author	Cheng Y Chen J Pourdehnad M Zhou S Li Y
author_facet	Cheng Y Chen J Pourdehnad M Zhou S Li Y
author_sort	Cheng Y
title	Population Pharmacokinetics of CC-122
title_short	Population Pharmacokinetics of CC-122
title_full	Population Pharmacokinetics of CC-122
title_fullStr	Population Pharmacokinetics of CC-122
title_full_unstemmed	Population Pharmacokinetics of CC-122
title_sort	population pharmacokinetics of cc-122
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/057f02a8d2314ce997e30bc610a5447f
work_keys_str_mv	AT chengy populationpharmacokineticsofcc122 AT chenj populationpharmacokineticsofcc122 AT pourdehnadm populationpharmacokineticsofcc122 AT zhous populationpharmacokineticsofcc122 AT liy populationpharmacokineticsofcc122
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Population Pharmacokinetics of CC-122

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