Berntorp E
Department for Coagulation Disorders, Malmö University Hospital, Sweden.
Acta Haematol. 1995;94 Suppl 1:8-11. doi: 10.1159/000204021.
Five purified concentrates--Nanotiv (Kabi Pharmacia), Immunine (Immuno), Factor IX VHP (Biotransfusion), Alphanine (Alpha Therapeutic Corporation), and Mononine (Armour Pharmaceutical Company)--were characterized biochemically and their in vivo pharmacokinetic and thrombogenic properties evaluated. The results were compared with those for two prothrombin complex concentrates (PCCs): Preconativ (Kabi Pharmacia) and Prothromplex TIM4 (Immuno). The measured values for factor IX coagulant activity (FIX:C) generally agreed with the manufacturers' labeled values. The purified concentrates were virtually devoid of other vitamin K-dependent coagulation factors, the inhibitor proteins C and S, and either fibrinogen, fibronectin, or immunoglobulins. Indicators of thrombin generation (i.e., prothrombin fragments F1 + 2 and thrombin-antithrombin complex) were present in varying amounts in all preparations. The level of specific activity in the purified concentrates exceeded that in the PCCs by a factor of 50- to 100-fold. Pharmacokinetic variables were studied in severe hemophilia B patients: Nanotiv was compared with Preconativ; Immunine was compared with Prothromplex TIM4 in crossover studies; and Mononine was tested in a single-drug study. No differences were apparent between Nanotiv, Preconativ, and Mononine, but recovery rates were lower, clearance rates higher, and FIX:C half-life shorter for Immunine and Prothromplex TIM4, although the disparate results might have been attributable to methodologic differences. Purified factor IX concentrates were used successfully as cover for surgery and in immune tolerance induction without observable adverse effects.
对五种纯化浓缩物——纳米替（卡比 Pharmacia 公司）、免疫宁（Immuno 公司）、凝血因子 IX VHP（生物输血公司）、α 因子（阿尔法治疗公司）和单凝血因子（装甲制药公司）——进行了生化特性鉴定，并评估了它们在体内的药代动力学和血栓形成特性。将结果与两种凝血酶原复合物浓缩物（PCCs）：普瑞康奈（卡比 Pharmacia 公司）和凝血酶原复合物 TIM4（Immuno 公司）的结果进行了比较。凝血因子 IX 凝血活性（FIX:C）的测量值总体上与制造商标注的值一致。纯化浓缩物几乎不含其他维生素 K 依赖性凝血因子、抑制蛋白 C 和 S，以及纤维蛋白原、纤连蛋白或免疫球蛋白。所有制剂中均存在不同量的凝血酶生成指标（即凝血酶原片段 F1 + 2 和凝血酶 - 抗凝血酶复合物）。纯化浓缩物中的比活性水平比 PCCs 高出 50 至 100 倍。在重度 B 型血友病患者中研究了药代动力学变量：在交叉研究中，将纳米替与普瑞康奈进行比较；将免疫宁与凝血酶原复合物 TIM4 进行比较；对单凝血因子进行了单药研究。纳米替、普瑞康奈和单凝血因子之间没有明显差异，但免疫宁和凝血酶原复合物 TIM4 的回收率较低、清除率较高且 FIX:C 半衰期较短，尽管这些不同结果可能归因于方法学差异。纯化的凝血因子 IX 浓缩物成功用于手术覆盖和免疫耐受诱导，未观察到不良反应。
