Abatacept

Abatacept (CTLA4lg) is a soluble fusion protein consisting of the extra-cellular domain of human CTLA4 and a fragment of the Fc portion of human IgG1 (hinge and CH2 and 3 domains). Abatacept is a selective T-cell co-stimulation modulator and a protein agent for the autoimmune diseases . In Vivo Abatacept reduces paw edema, and the SC Multiple-dose group shows significantly greater (t obs = 2.50) paw edema reduction compared with the IV dose group. ? Abatacept exhibits linear PK across the studied doses. The NCA clearance (CL) is 20.8 mL/day/kg, volume (V ss ) is 146 mL/kg, and bioavailability (F) of the SC dose dosing is 57.7%. ? Abatacept (oral; 10 mg/kg; every 2 days) reduces the proportion of activated T cells (CD44highCD62L–) and inhibits the up-regulation of ICOS and CD71 in homozygous DO11.10 RAG-2 –/– BALB/c (H-2d/d) mice. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Lewis rats (6-9 weeks old) with weights of 150-175 gDosage: 10 mg/kg (IV), 20 mg/kg (SC single-dose), 20 mg/kg (SC Multiple-dose) on day 21 with 10 mg/kg SC doses on days 23, 25, 27, and 29 Administration: IV or SC Result: Reduced paw edema, and the SC Multiple-dose group showed significantly greater (t obs = 2.50) paw edema reduction compared with the IV dose group. Animal Model: Male Lewis rats (6-9 weeks old) with weights of 150-175 gDosage: 10 mg/kg (IV), 20 mg/kg (SC single-dose), 20 mg/kg (SC Multiple-dose) on day 21 with 10 mg/kg SC doses on days 23, 25, 27, and 29 (Pharmacokinetic Study) Administration: IV or SC Result: The NCA clearance (CL) is 20.8 mL/day/kg, volume (V ss ) is 146 mL/kg, and bioavailability (F) of the SC dose dosing is 57.7%. Form:Solid

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