Abatacept (CTLA4lg) 是一種可溶性融合蛋白,由人 CTLA4 的胞外結(jié)構(gòu)域和人 IgG1 Fc 部分的片段 (鉸鏈,CH2 和 3 結(jié)構(gòu)域) 組成。Abatacept 是選擇性 T 細(xì)胞共刺激調(diào)節(jié)劑,也是一種用于自身免疫性疾病的蛋白藥物。
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.
Animal Model:
|
Male Lewis rats (6-9 weeks old) with weights of 150-175 g
|
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 (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 g
|
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 (V
ss
) is 146 mL/kg, and bioavailability (F) of the SC dose dosing is 57.7%.
|