Castleman disease (Also known as giant or angiofollicular lymph node hyperplasia, lymphoid hamartoma, or angiofollicular lymph node hyperplasia) is an abnormal non-cancerous growth of the lymph node that can resemble lymphomas. It is contributed to by hyperproliferation of cytokine-producing lymphocytes. Castleman disease can be unicentric (involving a single lymph node) or multicentric (systemic). Siltuximab is approved for the multi centric disease. Overproduction of IL-6 has been linked to systemic manifestations in patients with MCD.
Siltuximab is a chimeric (human and mouse) anti-IL6 antibody. It binds human IL-6 thus preventing the interaction of IL-6 to both soluble and membrane- bound IL-6 receptors.
The target, Interleukin-6 (IL6; Uniprot = P05231; ChEMBL = CHEMBL1795129 ; canSAR = P05231)is an pro-inflammatory cytokine produced by T-lymphocytes and macrophages in response to infection or trauma.
Siltuximab is produced in Chinese hamster ovary (CHO) cells and dministered as an 11 mg/kg dose given over 1 hour by intravenous infusion every 3 weeks. The maximum serum concentration (Cmax) was observed close to the end of infusion. At steady state, the serum mean Cmax value is 332 mcg/mL (42% CV), and the serum mean predose trough value is 84 mcg/mL (78% CV). The mean terminal half-life (t1/2) in patients after the first intravenous infusion of 11 mg/kg is 20.6 days, and clearance is 0.23 L/day (51% CV.
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