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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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Detalles Bibliográficos
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
Descripción
Sumario: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.