Comparative Study of the Anti-leukemic Effects of Imatinib Mesylate, Glivec™ Tablet and Its Generic Formulation, OHK9511
Comparative Study of the Anti-leukemic Effects of Imatinib Mesylate, Glivec™ Tablet and Its Generic Formulation, OHK9511
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DOI：
10.1248/bpb.b14-00652
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发表时间：
2015-03-01
影响因子：
2
通讯作者：
Kimura, Shinya
中科院分区：
文献类型：
--
作者：
Yokoo, Masako;Kubota, Yasushi;Kimura, Shinya
甲磺酸伊马替尼(IM)的长期治疗使慢性粒细胞白血病(CML)患者的寿命接近正常。然而，包括IM在内的酪氨酸激酶抑制剂极其昂贵的事实是导致依从性差的一个主要原因，导致疾病复发或耐药性。因此，鼓励医生开仿制药，以减轻医疗费用的经济负担。在日本，只有基本化学结构和药代动力学数据与原始药物相同的仿制药才能获得批准。然而，并不是必须证明仿制药具有足够的生物效应。这是日本血液学家不经常使用普通IM的原因之一。本研究的目的是比较Glivec(TM)(一种商业IM)及其仿制制剂OHK9511的抗白血病作用。OHK9511和Glivec(TM)的IC50值相似，均可诱导几种CML细胞株发生凋亡。此外，移植了bcr-abl阳性细胞的OHK9511治疗的小鼠的总体存活率与Glivec(TM)治疗的小鼠相似。虽然这里进行的实验是基本的，但结果表明医生应该考虑使用通用IM。
Long-term treatment with imatinib mesylate (IM) allows patients with chronic myeloid leukemia (CML) to live a near-normal lifespan. However, the fact that tyrosine kinase inhibitors, including IM, are extremely expensive is a major cause of poor adherence, resulting in disease relapse or drug resistance. Therefore, physicians are encouraged to prescribe generic drugs to reduce the financial burden of medical expenses. In Japan, only generic drugs that have a basic chemical structure and pharmacokinetic data that are the same as those of the original drug are approved. However, it is not mandatory to demonstrate that generic drugs have adequate biological effects. This is one of the reasons why Japanese hematologists do not often use generic IM. The aim of the present study was to compare the anti-leukemic effects of Glivec (TM) (a commercial IM) and its generic formulation, OHK9511. The IC50 values of OHK9511 and Glivec (TM) were comparable, and both induced similar levels of apoptosis in several CML cell lines. Furthermore, the overall survival of OHK9511-treated mice transplanted with BCR-ABL-positive cells was similar to that of mice treated with Glivec (TM). Although the experiments performed herein were basic, the results suggest that physicians should consider using generic IM.