Population pharmacokinetics of siltuximab: impact of disease state
| Autor: | Edmund V. Capparelli, Mina Nikanjam, Jin Yang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Adolescent Population Renal function Antineoplastic Agents Disease Toxicology Models Biological Gastroenterology Article Siltuximab Young Adult 03 medical and health sciences chemistry.chemical_compound Clinical Trials Phase II as Topic 0302 clinical medicine Pharmacokinetics Neoplasms Internal medicine Humans Medicine Pharmacology (medical) Dosing education Serum Albumin Aged Aged 80 and over Pharmacology education.field_of_study Clinical Trials Phase I as Topic business.industry Castleman Disease Albumin Antibodies Monoclonal Middle Aged Clinical trial 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Female business Monte Carlo Method Half-Life |
| Zdroj: | Cancer Chemother Pharmacol |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | 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 7 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. |
| Databáze: | OpenAIRE |
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