Dose selection of siltuximab for multicentric Castleman’s disease
| العنوان: | Dose selection of siltuximab for multicentric Castleman’s disease |
|---|---|
| المؤلفون: | Lanyi Xie, Helgi van de Velde, Ming Qi, Manjula Reddy, Hugh M. Davis, Rajesh Bandekar, Christina Lourdes Mayer, Thomas A. Puchalski, Xiang Qin |
| المصدر: | Cancer Chemotherapy and Pharmacology. 75:1037-1045 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, medicine.drug_class, Multicentric Castleman's disease, Antineoplastic Agents, Toxicology, Monoclonal antibody, Models, Biological, Siltuximab, chemistry.chemical_compound, Pharmacokinetics, Internal medicine, medicine, Humans, Pharmacology (medical), Infusions, Intravenous, Aged, Randomized Controlled Trials as Topic, Pharmacology, Dose-Response Relationship, Drug, biology, business.industry, Castleman Disease, Antibodies, Monoclonal, Interleukin, Middle Aged, chemistry, Pharmacodynamics, Immunology, biology.protein, Antibody, business, Dose selection |
| الوصف: | Siltuximab is a monoclonal antibody that binds to interleukin (IL)-6 with high affinity and specificity; C-reactive protein (CRP) is an acute-phase protein induced by IL-6. CRP suppression is an indirect measurement of IL-6 activity. Here, modeling and simulation of the pharmacokinetic (PK)/pharmacodynamic (PD) relationship between siltuximab and CRP were used to support dose selection for multicentric Castleman's disease (CD).PK/PD modeling was applied to explore the relationship between siltuximab PK and CRP suppression following intravenous siltuximab infusion in 47 patients with B cell non-Hodgkin's lymphoma (n = 17), multiple myeloma (n = 13), or CD (n = 17). Siltuximab was administered as 2.8, 5.5, or 11 mg/kg q2wks, 11 mg/kg q3wks, or 5.5 mg/kg weekly. Simulations of studied or hypothetical siltuximab dosage regimens (15 mg/kg q4wks) were also performed to evaluate maintenance of CRP suppression below the cutoff value of 1 mg/L.A two-compartment PK model and an inhibitory indirect response PD model adequately described the serum siltuximab and CRP concentration-time profiles simultaneously. PD parameter estimates were physiologically plausible. For all disease types, simulations showed that 11 mg/kg q3wks or 15 mg/kg q4wks would reduce serum CRP to below 1 mg/L after the second dose and throughout the treatment period.PK/PD modeling was used to select doses for further development of siltuximab in multicentric CD. The dosing recommendation was also supported by the observed efficacy dose-response relationship. CRP suppression in the subsequent randomized multicentric CD study was in agreement with the modeling predictions. |
| تدمد: | 1432-0843 0344-5704 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a13180d84eef213ae5f31e6cdd7f935Test https://doi.org/10.1007/s00280-015-2720-0Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....0a13180d84eef213ae5f31e6cdd7f935 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320843 03445704 |
|---|