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Population Pharmacokinetics of CC-122

BACKGROUND: 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 populati...

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Autores principales: Cheng, Yiming, Chen, Jian, Pourdehnad, Michael, Zhou, Simon, Li, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093142/
https://www.ncbi.nlm.nih.gov/pubmed/33958900
http://dx.doi.org/10.2147/CPAA.S310604
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author Cheng, Yiming
Chen, Jian
Pourdehnad, Michael
Zhou, Simon
Li, Yan
author_facet Cheng, Yiming
Chen, Jian
Pourdehnad, Michael
Zhou, Simon
Li, Yan
author_sort Cheng, Yiming
collection PubMed
description BACKGROUND: 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.
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spelling pubmed-80931422021-05-05 Population Pharmacokinetics of CC-122 Cheng, Yiming Chen, Jian Pourdehnad, Michael Zhou, Simon Li, Yan Clin Pharmacol Original Research BACKGROUND: 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. Dove 2021-04-28 /pmc/articles/PMC8093142/ /pubmed/33958900 http://dx.doi.org/10.2147/CPAA.S310604 Text en © 2021 Cheng et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Cheng, Yiming
Chen, Jian
Pourdehnad, Michael
Zhou, Simon
Li, Yan
Population Pharmacokinetics of CC-122
title 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_short Population Pharmacokinetics of CC-122
title_sort population pharmacokinetics of cc-122
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093142/
https://www.ncbi.nlm.nih.gov/pubmed/33958900
http://dx.doi.org/10.2147/CPAA.S310604
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