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目的研究多次静脉滴注重组人CTLA4-抗体融合蛋白在类风湿关节炎病人体内的药动学。方法选择9例类风湿关节炎病人,年龄(50±s12)岁,在(60±5)min内匀速静脉滴注重组人CTLA4-抗体融合蛋白,每次10mg·kg-1,共给药6次,用酶联免疫吸附法(ELISA)测定人血清中各点CTLA4-Ig浓度。采用DAS2.1.1软件进行数据处理,计算药动学参数。结果受试者多次静脉滴注重组人CTLA4-抗体融合蛋白,按非房室模型计算,主要药动学参数t1/2为(13±5)d,ρssmax为(247±50)mg·L-1,tssmax为(0.06±0.04)d,AUCss为(1830±708)mg·d·L-1,Vss为(0.07±0.03)L·kg-1,DF为(3.5±1.6)。受试者在给药期间未出现严重不良反应。结论在给药后第4次时重组人CTLA4-抗体融合蛋白血药浓度可达到稳态,连续给药6次后体内未见蓄积,该方案适宜在临床推广使用。
Objective To study the pharmacokinetics of intravenous recombinant human CTLA4-antibody fusion protein in patients with rheumatoid arthritis. Methods Nine patients with rheumatoid arthritis were selected and aged (50 ± s12) years old. Intravenous infusion of recombinant human CTLA4-antibody fusion protein (10 mg · kg-1) Times, the concentration of CTLA4-Ig in each point of human serum was determined by enzyme-linked immunosorbent assay (ELISA). Using DAS2.1.1 software for data processing, calculation of pharmacokinetic parameters. Results The subjects were repeatedly intravenous infusion of recombinant human CTLA4-antibody fusion protein, non-compartmental model calculations, the main pharmacokinetic parameters t1 / 2 (13 ± 5) d, ρssmax (247 ± 50) mg · L (0.06 ± 0.04) d, AUCss of (1830 ± 708) mg · d · L-1, Vss of (0.07 ± 0.03) L · kg-1 and DF of 3.5 ± 1.6. Subjects did not experience serious adverse reactions during the dosing period. Conclusion The plasma concentration of recombinant human CTLA4-antibody fusion protein reached the steady state at the 4th post-administration, and no accumulation was observed in vivo after 6 consecutive administrations. This protocol is suitable for clinical use.