Ohnishi Kunihiko, Kawaguchi Atsuhiro, Nakajima Shunji, Mori Hiroyuki, Ueshima Takahiro
Ohnishi Hospital, Saitama, Japan.
J Clin Pharmacol. 2008 Feb;48(2):203-8. doi: 10.1177/0091270007310549.
We conducted an open-label, parallel-group study of the high purity, mass-produced recombinant human serum albumin (rHSA), derived from the methylotrophic yeast Pichia pastoris, to compare pharmacokinetics and ensure bioequivalence with plasma-derived human serum albumin (pHSA) in 22 patients with liver cirrhosis. Both rHSA and pHSA groups enrolled 11 patients each, assigned according to predose serum albumin concentrations using the minimization method. Pharmacokinetic and safety profiles for 3-day repeated intravenous infusions at a daily dose of 25 g were evaluated for 8 days. Geometric mean AUC(0-168hr) (g.hr/dL) was 637.12 and 635.93 in the rHSA and pHSA groups, respectively, with a 90% confidence interval (CI) for the difference (92.9%-108.1%) lying within the bioequivalence range. The other major parameter, geometric mean C(max) (g/dL), was 4.16 and 4.19 in the rHSA and pHSA groups, respectively, with a 90% CI for the difference (92.7%-106.4%). The pHSA group presented with 3 adverse events: 1 case of insomnia, and 2 laboratory abnormalities with no serious adverse events. Results from this study show similar pharmacokinetic profiles following intravenous administration of 25g/day of rHSA and pHSA for 3 days, indicating bioequivalence.
我们开展了一项开放标签、平行组研究,以比较高纯度、大规模生产的源自甲基营养型酵母毕赤酵母的重组人血清白蛋白(rHSA)与血浆源性人血清白蛋白(pHSA)的药代动力学,并确保其在22例肝硬化患者中的生物等效性。rHSA组和pHSA组各纳入11例患者,采用最小化法根据给药前血清白蛋白浓度进行分配。对每日剂量25 g、连续3天重复静脉输注的药代动力学和安全性进行了8天的评估。rHSA组和pHSA组的几何平均AUC(0 - 168hr)(g·hr/dL)分别为637.12和635.93,差异的90%置信区间(CI)(92.9% - 108.1%)在生物等效范围内。另一个主要参数,几何平均C(max)(g/dL),rHSA组和pHSA组分别为4.16和4.19,差异的90% CI为(92.7% - 106.4%)。pHSA组出现3例不良事件:1例失眠,2例实验室异常,无严重不良事件。本研究结果表明,每日静脉注射25g rHSA和pHSA,连续3天,药代动力学特征相似,表明具有生物等效性。