Zadaxin Mechanism of Action

Pharmacology: The mechanism of action of Zadaxin is not completely understood but is thought to be related to its immunomodulating activities, centered primarily around augmentation of T-cell function. In various in vitro assays, thymosin α₁ has been shown to promote T-cell differentiation and maturation eg, CD4+, CD8+ and CD3+ cells have all been shown to be increased. Thymosin α₁ has also been shown to increase production of IFN-γ, IL-2, IL-3, and expression of IL-2 receptor following activation by mitogens or antigens, increase NK cell activity, increase production of migratory inhibitory factor (MIF) and increase antibody response to T-cell dependent antigens. Thymosin α₁ has also been shown to antagonize dexamethasone-induced apoptosis of thymocytes in vitro. In vivo administration of thymosin α₁ to animals immunosuppressed by chemotherapy, tumor burden, or irradiation showed that thymosin α₁ protects against cytotoxic damage to bone marrow, tumor progression and opportunistic infections, thereby increasing survival time and number of survivors. Many of the in vitro and in vivo effects of thymosin α₁ have been interpreted as influences on either differentiation of pluripotent stem cells to thymocytes or activation of thymocytes into activated T-cells.
Pharmacokinetics: The pharmacokinetics of thymosin α₁ were studied in adult volunteers at single SC doses ranging from 0.8-6.4 mg and in multiple-dose studies of 5-7 days' duration at SC doses ranging from 1.6-16 mg. Thymosin α₁ was rapidly absorbed with peak serum levels achieved at approximately 2 hrs. A dose proportional increase was seen in serum levels for C_max and AUC, and serum levels returned to basal levels by 24 hrs after administration. The serum half-life was approximately 2 hrs and there was no evidence of accumulation following multiple SC doses. Urine excretion ranged from 31-60% of the administered dose following single and multiple doses.