Di Paola J, Smith M P, Klamroth R, Mannucci P M, Kollmer C, Feingold J, Kessler C, Pollmann H, Morfini M, Udata C, Rothschild C, Hermans C, Janco R
University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Haemophilia. 2007 Mar;13(2):124-30. doi: 10.1111/j.1365-2516.2006.01420.x.
ReFacto is a recombinant B-domain-deleted, monoclonal antibody-purified, solvent-detergent-treated factor VIII (BDDrFVIII) with no albumin added to the final formulation. Although ReFacto has been shown to be bioequivalent to a plasma-derived FVIII product (Hemophil-M) in a randomized, crossover pharmacokinetic (PK) study, the comparability of ReFacto with the full-length (complete sequence) recombinant FVIII (FLrFVIII, Advate) product has not been previously examined in this manner. The primary objective of this study was to compare the PKs of ReFacto with those of Advate in patients with severe haemophilia A. This was a third-party unblinded, randomized, multicentre, two-period crossover PKs study of ReFacto and Advate in subjects with severe haemophilia A (FVIII:C < or =1%). Blood samples were collected over a 48-h period after i.v. administration of each of the FVIII products. FVIII:C was determined using the chromogenic substrate assay (CSA) in a central laboratory. The plasma FVIII:C PK parameters of ReFacto and Advate were determined using non-compartmental analysis. Bioequivalence was assessed on maximum plasma concentration (C(max)) and the area under the plasma concentration vs. time curves (AUCs) using an anova. The two products were judged to be equivalent if the 90% confidence limits of the ratio of the geometric mean values of C(max) and AUCs fell within the interval of 80-125%. Results from this PKs comparison of two different rFVIII products, using chromogenic substrate assay to measure FVIII:C, showed that ReFacto and Advate are bioequivalent to each other.
瑞友维（ReFacto）是一种重组的、去除B结构域的、单克隆抗体纯化的、经溶剂去污剂处理的凝血因子VIII（BDDrFVIII），最终制剂中未添加白蛋白。尽管在一项随机交叉药代动力学（PK）研究中已证明瑞友维与血浆源性FVIII产品（Hemophil-M）具有生物等效性，但此前尚未以这种方式检验瑞友维与全长（完整序列）重组FVIII（FLrFVIII，阿凡特（Advate））产品的可比性。本研究的主要目的是比较重度A型血友病患者中瑞友维与阿凡特的药代动力学。这是一项针对重度A型血友病（FVIII:C≤1%）受试者的瑞友维和阿凡特的第三方非盲、随机、多中心、两期交叉药代动力学研究。在静脉注射每种FVIII产品后的48小时内采集血样。在中心实验室使用发色底物法（CSA）测定FVIII:C。使用非房室分析确定瑞友维和阿凡特的血浆FVIII:C药代动力学参数。使用方差分析评估最大血浆浓度（C(max)）和血浆浓度-时间曲线下面积（AUCs）的生物等效性。如果C(max)和AUCs几何平均值之比的90%置信限落在80-125%的区间内，则判定这两种产品等效。使用发色底物法测量FVIII:C对两种不同重组FVIII产品进行药代动力学比较的结果表明，瑞友维和阿凡特彼此具有生物等效性。
