血浆源性与重组因子 IX 在乙型血友病患者中的药代动力学和药效学特性：一项前瞻性交叉研究。

Pharmacokinetic and pharmacodynamic properties of plasma-derived vs. recombinant factor IX in patients with hemophilia B: a prospective crossover study.

机构信息

Centre for Haemostasis and Thrombosis, Guy's and St Thomas' NHS Foundation Trust, London, UK.

出版信息

J Thromb Haemost. 2014 Dec;12(12):2044-8. doi: 10.1111/jth.12756. Epub 2014 Nov 11.

DOI:10.1111/jth.12756

PMID:25315324

Abstract

BACKGROUND

Effective treatment of acute bleeding episodes in patients with hemophilia B relies on factor IX recovery, with higher levels being more desirable, whereas prevention of bleeds with a prophylactic regimen depends on the half-life of the product. Lower recovery values have been reported following administration of recombinant FIX (rFIX) than following administration of plasma-derived FIX (pdFIX).

OBJECTIVES

To compare the pharmacokinetic and pharmacodynamic properties of rFIX and pdFIX in patients with hemophilia B.

METHODS

A prospective crossover study of nine patients with moderate to severe hemophilia B was performed. Following a washout period, 50 U kg(-1) FIX was administered, and blood samples were taken as per protocol up to 48 h postinfusion. Paired data were analyzed with the Wilcoxon signed rank test.

RESULTS

Mean peak recovery at 10 min postinfusion was 62.14 IU dL(-1) with pdFIX and 52.7 IU dL(-1) with rFIX (P = 0.08). Mean half-life was 16.6 h with pdFIX and 17.5 h with rFIX (P = 0.55). Maximum peak thrombin generation (PTG) was 35.9 nm with pdFIX and 28.9 nm with rFIX (P = 0.21). Administration of rFIX resulted in early PTG, whereas administration of pdFIX resulted in slightly later and sustained PTG. At 48 h, PTG was similar with pdFIX (19.0 nm) and rFIX (19.4 nm) (P = 0.91).

CONCLUSIONS

Patients experienced better recovery with pdFIX than with rFIX. pdFIX and rFIX had similar half-lives. Maximum PTG was higher for pdFIX; however, this difference did not reach statistical significance. The clinical impact of the slightly increased, delayed and sustained PTG with pdFIX requires further investigation.

摘要

背景

乙型血友病患者急性出血发作的有效治疗依赖于凝血因子 IX 的恢复，水平越高越理想，而预防性治疗方案则取决于产品的半衰期。与血浆源性凝血因子 IX（pdFIX）相比，重组凝血因子 IX（rFIX）给药后恢复值较低。

目的

比较乙型血友病患者 rFIX 和 pdFIX 的药代动力学和药效动力学特性。

方法

对 9 名中重度乙型血友病患者进行前瞻性交叉研究。在洗脱期后，给予 50 U kg(-1)FIX，根据方案在输注后 48 小时内采血。采用 Wilcoxon 符号秩检验对配对数据进行分析。

结果

pdFIX 给药后 10 分钟平均峰值恢复为 62.14 IU dL(-1)，rFIX 为 52.7 IU dL(-1)（P = 0.08）。pdFIX 的平均半衰期为 16.6 小时，rFIX 为 17.5 小时（P = 0.55）。pdFIX 的最大峰值凝血酶生成（PTG）为 35.9 nm，rFIX 为 28.9 nm（P = 0.21）。rFIX 给药后早期出现 PTG，而 pdFIX 给药后出现稍晚但持续的 PTG。在 48 小时时，pdFIX（19.0 nm）和 rFIX（19.4 nm）的 PTG 相似（P = 0.91）。