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- Title
Population pharmacokinetics of siltuximab: impact of disease state.
- Authors
Nikanjam, Mina; Yang, Jin; Capparelli, Edmund V.
- Abstract
<bold>Purpose: </bold>To characterize the effects of disease type and clinical characteristics on the pharmacokinetics of siltuximab, an IL-6 inhibiting monoclonal antibody.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Albumin and disease state are important factors for siltuximab disposition and will likely need to be considered for dosing in future therapeutic applications.
- Subjects
MONTE Carlo method; CASTLEMAN'S disease; PHARMACOKINETICS; DISEASE progression; MONOCLONAL antibodies; ALBUMINS
- Publication
Cancer Chemotherapy & Pharmacology, 2019, Vol 84, Issue 5, p993
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-019-03939-7