Population pharmacokinetics of siltuximab : impact of disease state
PURPOSE: To characterize the effects of disease type and clinical characteristics on the pharmacokinetics of siltuximab, an IL-6 inhibiting monoclonal antibody.
METHODS: Siltuximab pharmacokinetic data were combined from seven phase I/II clinical trials. A population pharmacokinetic model was developed to characterize changes in siltuximab disposition with disease type, albumin, liver and renal function, and patient demographics.
RESULTS: A total of 7761 concentrations from 460 participants were used in the study. The data were well described by a two-compartment model. Castleman's disease, healthy volunteer status, albumin, and ALT were independent predictors of clearance. Monte Carlo simulations of the final model for an 11 mg/kg dose resulted in a longer median half-life for healthy volunteers (24.5 days) as compared to Castleman's disease (19.1 days) and other tumor types (22.2 days). Clearance varied 1.8-fold over the range of albumin values seen in the study (1.5-5.2 g/dL), while ALT resulted in minimal changes in clearance.
CONCLUSIONS: Albumin and disease state are important factors for siltuximab disposition and will likely need to be considered for dosing in future therapeutic applications.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:84 |
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| Enthalten in: |
Cancer chemotherapy and pharmacology - 84(2019), 5 vom: 03. Nov., Seite 993-1001 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nikanjam, Mina [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal |
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| Anmerkungen: |
Date Completed 19.05.2020 Date Revised 11.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00280-019-03939-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM300913524 |
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| 100 | 1 | |a Nikanjam, Mina |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Population pharmacokinetics of siltuximab |b impact of disease state |
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| 500 | |a Date Completed 19.05.2020 | ||
| 500 | |a Date Revised 11.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: To characterize the effects of disease type and clinical characteristics on the pharmacokinetics of siltuximab, an IL-6 inhibiting monoclonal antibody | ||
| 520 | |a METHODS: Siltuximab pharmacokinetic data were combined from seven phase I/II clinical trials. A population pharmacokinetic model was developed to characterize changes in siltuximab disposition with disease type, albumin, liver and renal function, and patient demographics | ||
| 520 | |a RESULTS: A total of 7761 concentrations from 460 participants were used in the study. The data were well described by a two-compartment model. Castleman's disease, healthy volunteer status, albumin, and ALT were independent predictors of clearance. Monte Carlo simulations of the final model for an 11 mg/kg dose resulted in a longer median half-life for healthy volunteers (24.5 days) as compared to Castleman's disease (19.1 days) and other tumor types (22.2 days). Clearance varied 1.8-fold over the range of albumin values seen in the study (1.5-5.2 g/dL), while ALT resulted in minimal changes in clearance | ||
| 520 | |a CONCLUSIONS: Albumin and disease state are important factors for siltuximab disposition and will likely need to be considered for dosing in future therapeutic applications | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Castleman’s disease | |
| 650 | 4 | |a IL-6 | |
| 650 | 4 | |a Oncology | |
| 650 | 4 | |a Population pharmacokinetics | |
| 650 | 4 | |a Siltuximab | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Serum Albumin |2 NLM | |
| 650 | 7 | |a siltuximab |2 NLM | |
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| 700 | 1 | |a Yang, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Capparelli, Edmund V |e verfasserin |4 aut | |
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