Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenance
Background: Dosing of intravenous protein C concentrate (Ceprotin) in patients with protein C deficiency is guided by pharmacokinetics (PK) of plasma protein C activity. Objectives: This study aimed to characterize PK of intravenous Ceprotin in patients with severe congenital protein C deficiency (S...
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Elsevier
2025-03-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037925001839 |
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| author | Zhaoyang Li Inmaculada C. Sorribes Jennifer Schneider Adekemi Taylor |
| author_facet | Zhaoyang Li Inmaculada C. Sorribes Jennifer Schneider Adekemi Taylor |
| author_sort | Zhaoyang Li |
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| description | Background: Dosing of intravenous protein C concentrate (Ceprotin) in patients with protein C deficiency is guided by pharmacokinetics (PK) of plasma protein C activity. Objectives: This study aimed to characterize PK of intravenous Ceprotin in patients with severe congenital protein C deficiency (SCPCD) and severe acquired protein C deficiency (SAPCD). Methods: An exploratory analysis was conducted to assess effects of demographic and disease-related factors on PK of Ceprotin (n = 35 patients with SCPCD or SAPCD), followed by a population PK analysis on data from 4 prospective clinical trials of Ceprotin in SCPCD or SAPCD (n = 58). Model-based simulations were conducted across 3-stage or 1-stage dosing scenarios based on label-recommended doses in acute or maintenance settings. Results: Age, body weight, and symptomatic state of disease appeared to influence PK of Ceprotin, including endogenous production of (active) protein C. Model-based simulations predicted that after the first doses, 15% to 76% of patients in the 3-stage dosing scenarios (initial dose: 60-120 IU/kg) and 15% of patients in the 1-stage dosing scenario (60 IU/kg every 12 hours) would attain the recommended target Cmax of >100 IU/dL. At steady state, ≥86% of patients were predicted to attain the recommended maintenance Ctrough of >25 IU/dL. The steady-state protein C concentration was driven by the maintenance dose, regardless of the level of initial loading doses. Conclusion: Age, body weight, and symptomatic disease state should be considered in dose optimization. Model-based simulations support the use of various combined loading and maintenance regimens to quickly and effectively achieve target protein C plasma levels. |
| format | Article |
| id | doaj-art-b5acce1e7010411cb63df83bb71e3329 |
| institution | OA Journals |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-b5acce1e7010411cb63df83bb71e33292025-08-20T02:31:07ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-03-019310285910.1016/j.rpth.2025.102859Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenanceZhaoyang Li0Inmaculada C. Sorribes1Jennifer Schneider2Adekemi Taylor3Takeda Development Center Americas, Inc, Cambridge, Massachusetts, USA; Correspondence Zhaoyang Li, Clinical Pharmacology and Early Clinical Development, Plasma-Derived Therapy Business Unit, Takeda Pharmaceutical Company Limited, Takeda Development Center Americas, Inc, 650 East Kendall Street, Cambridge, MA 02142, USA.Certara, Inc, Radnor, Pennsylvania, USACertara, Inc, Radnor, Pennsylvania, USACertara, Inc, Radnor, Pennsylvania, USABackground: Dosing of intravenous protein C concentrate (Ceprotin) in patients with protein C deficiency is guided by pharmacokinetics (PK) of plasma protein C activity. Objectives: This study aimed to characterize PK of intravenous Ceprotin in patients with severe congenital protein C deficiency (SCPCD) and severe acquired protein C deficiency (SAPCD). Methods: An exploratory analysis was conducted to assess effects of demographic and disease-related factors on PK of Ceprotin (n = 35 patients with SCPCD or SAPCD), followed by a population PK analysis on data from 4 prospective clinical trials of Ceprotin in SCPCD or SAPCD (n = 58). Model-based simulations were conducted across 3-stage or 1-stage dosing scenarios based on label-recommended doses in acute or maintenance settings. Results: Age, body weight, and symptomatic state of disease appeared to influence PK of Ceprotin, including endogenous production of (active) protein C. Model-based simulations predicted that after the first doses, 15% to 76% of patients in the 3-stage dosing scenarios (initial dose: 60-120 IU/kg) and 15% of patients in the 1-stage dosing scenario (60 IU/kg every 12 hours) would attain the recommended target Cmax of >100 IU/dL. At steady state, ≥86% of patients were predicted to attain the recommended maintenance Ctrough of >25 IU/dL. The steady-state protein C concentration was driven by the maintenance dose, regardless of the level of initial loading doses. Conclusion: Age, body weight, and symptomatic disease state should be considered in dose optimization. Model-based simulations support the use of various combined loading and maintenance regimens to quickly and effectively achieve target protein C plasma levels.http://www.sciencedirect.com/science/article/pii/S2475037925001839intravenous protein C concentrateplasma protein C activitypopulation pharmacokineticsprotein C deficiencyreplacement therapy |
| spellingShingle | Zhaoyang Li Inmaculada C. Sorribes Jennifer Schneider Adekemi Taylor Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenance Research and Practice in Thrombosis and Haemostasis intravenous protein C concentrate plasma protein C activity population pharmacokinetics protein C deficiency replacement therapy |
| title | Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenance |
| title_full | Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenance |
| title_fullStr | Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenance |
| title_full_unstemmed | Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenance |
| title_short | Evaluation of pharmacokinetics of intravenous protein C concentrate in protein C deficiency: implications for treatment initiation and maintenance |
| title_sort | evaluation of pharmacokinetics of intravenous protein c concentrate in protein c deficiency implications for treatment initiation and maintenance |
| topic | intravenous protein C concentrate plasma protein C activity population pharmacokinetics protein C deficiency replacement therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2475037925001839 |
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