A review of nonclinical toxicology studies of becaplermin (rhPDGF-BB)
A review of nonclinical toxicology studies of becaplermin (rhPDGF-BB)
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DOI：
10.1016/s0002-9610(98)00176-7
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发表时间：
1998-08-01
影响因子：
3
通讯作者：
Dooley, J
中科院分区：
文献类型：
--
作者：
Knight, EV;Oldham, JW;Dooley, J
Becaplermin（重组人血小板衍生生长因子-BB [BB同型二聚体，rhPDGF-BB]）在一系列旨在评估其全身毒性、致敏性、局部刺激性和遗传毒性潜力的非临床研究中显示出良好的安全性特征。猴单次和多次静脉或皮下给予高达3 mg/kg的剂量后，未观察到直接归因于becaplermin的显著局部或全身毒性。小鼠单次大剂量静脉给药（高达100 mg/kg）和1或3 mg/kg重复给药导致快速可逆的血管舒张和中枢神经系统抑制。在一项骨毒性研究中，becaplermin产生的组织形态学变化提示骨重建加速，被判定为可能可逆。在人类中没有观察到类似的发现。尽管认为becaplermin不是皮肤或眼部刺激物，但在动物中观察到一些皮肤致敏作用;这一发现对于重组人源蛋白并不意外。在多种体外试验和一项体内试验中，贝卡普勒明无遗传毒性。美国外科杂志1998;176（增刊2A）：55 S-60 S。(C)1998年，Excerpta Medica，Inc.
Becaplermin (recombinant human platelet-derived growth factor-BB [BB homodimer, rhPDGF-BB]) has demonstrated a favorable safety profile in a series of nonclinical studies designed to assess its systemic toxicity, sensitization, local irritation, and genotoxic potential. No significant local or systemic toxicity directly attributable to becaplermin was observed following single and multiple intravenous or subcutaneous administration at doses up to 3 mg/kg in monkeys. Administration of single large intravenous doses (up to 100 mg/kg) and repeated dosing at 1 or 3 mg/kg in mice resulted in rapidly reversible vasodilation and central nervous system depression. In a bone-toxicity study, becaplermin produced histomorphologic changes suggestive of accelerated bone remodeling, which were judged to be potentially reversible. Similar findings have not been observed in humans. Although becaplermin was not considered a dermal or ocular irritant, some skin-sensitizing effects were observed in animals; this finding was not unexpected for a recombinant human-derived protein. Becaplermin was not genotoxic in a variety of in vitro assays and in one in vivo assay. Am J Surg. 1998;176(Suppl 2A):55S-60S. (C) 1998 by Excerpta Medica, Inc.