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)[1]. Abatacept is a selective T-cell co-stimulation modulator and a protein drug for the treatment of autoimmune diseases[2].

Signaling Pathways >> Others >> Others

Abatacept reduces paw edema, and the SC Multiple-dose group shows significantly greater (tobs = 2.50) paw edema reduction compared with the IV dose group[2]. Abatacept exhibits linear PK across the studied doses. The NCA clearance (CL) is 20.8 mL/day/kg, volume (Vss) is 146 mL/kg, and bioavailability (F) of the SC dose dosing is 57.7%[2]. 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[3]. Animal Model: Male Lewis rats (6-9 weeks old) with weights of 150-175 g[2] Dosage: 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 (tobs = 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 g[2] Dosage: 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 (Vss) is 146 mL/kg, and bioavailability (F) of the SC dose dosing is 57.7%.

[1]. Kiykim A, et al. Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency. J Allergy Clin Immunol Pract. 2019 Jun 22.

[2]. Lon HK, et al. Modeling pharmacokinetics/pharmacodynamics of abatacept and disease progression in collagen-induced arthritic rats: a population approach. J Pharmacokinet Pharmacodyn. 2013 Dec;40(6):701-12.

[3]. Patakas A, et al. Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen-Presenting Cells. Arthritis Rheumatol. 2016 Mar;68(3):627-38.