Haselbeck Anton
Roche Diagnostics GmbH, D-82372 Penzberg, Germany.
Curr Med Res Opin. 2003;19(5):430-2. doi: 10.1185/030079903125002063.
Recombinant human erythropoietin (epoetin) is a highly active molecule and as such is used at very low therapeutic concentrations that require stabilisation. Commercially available epoetins differ in the stabilisers used in their formulations, which result in variations between epoetin preparations in storage and handling requirements. The stability and solubility of the epoetins are also affected by differences in the carbohydrate moieties that exist between them. However, it is the difference in stabilising agents that is thought to be the major cause of the upsurge in pure red cell aplasia (PRCA) cases observed predominantly with one epoetin alfa formulation, Eprex (Johnson & Johnson). In 1998 the European formulation of Eprex was changed with the replacement of human serum albumin (HSA), by polysorbate 80 and glycine. This formulation change coincided with an increased incidence of PRCA. In contrast, the incidence of PRCA has remained low with other HSA-containing epoetin alfa products and with epoetin beta. Therefore, it appears that the change in Eprex formulation has resulted in reduced protein stability and increased immunogenicity.
重组人促红细胞生成素（促红素）是一种高活性分子，因此在需要稳定化的极低治疗浓度下使用。市售促红素在其制剂中使用的稳定剂有所不同，这导致促红素制剂在储存和处理要求方面存在差异。促红素的稳定性和溶解性也受到它们之间存在的碳水化合物部分差异的影响。然而，人们认为稳定剂的差异是主要观察到的纯红细胞再生障碍性贫血（PRCA）病例激增的主要原因，这种情况主要发生在一种促红细胞生成素α制剂，即益比奥（强生公司）中。1998年，欧洲版的益比奥进行了配方更改，用人造山梨醇酯80和甘氨酸取代了人血清白蛋白（HSA）。这一配方更改与PRCA发病率的增加同时出现。相比之下，其他含HSA的促红细胞生成素α产品和促红细胞生成素β的PRCA发病率一直较低。因此，益比奥配方的改变似乎导致了蛋白质稳定性降低和免疫原性增加。
