摘要
慢性粒细胞性白血病(CML)和费城染色体阳性急性淋巴细胞白血病(Ph+ALL),是由Bcr-Abl癌基因引起的。伊马替尼能抑制Bcr-Abl蛋白酪氨酸激酶活性,是一种有效的治疗慢性期CML的药物,但由于其耐药点突变,使加速期或急变期CML和Ph+ALL患者常常复发。尼罗替尼是第2代Bcr-Abl激酶抑制剂,效果比伊马替尼强20倍,对伊马替尼耐药和不能耐受的患者(T315 I除外)有广泛的活性。I/II期临床试验表明,尼罗替尼对伊马替尼耐药或不能耐受的CML患者仍能获得血液学和细胞遗传学的缓解。现对尼罗替尼的药理作用、药动学、药物相互作用、安全性进行综述。
Chronic myelogenous leukaemia（CML） and Philadelphia chromosome positive（Ph＋） acute lymphoblastic leukaemia（ALL） are caused by the Bcr-Abl oncogene.Imatinib inhibits the tyrosine kinase activity of the Bcr-Abl protein,and is an effective therapeutic agent for chronic-phase CML.However,accelerated or blast-crisis phase CML patients and Ph＋ ALL patients often relapse due to drug resistance resulting from the emergence of imatinib-resistant point mutations.Nilotinib is a second-generation tyrosine kinase inhibitor with 20-fold higher potency against Bcr-Abl kinase than imatinib.Notably,nilotinib is active in a wide range of imatinib-resistant or-intolerant patients,except for T315I.In phase I/II clinical trials,nilotinib has shown haematological and cytogenetic responses in CML patients,who either did not initially respond to imatinib or developed imatinib resistance.In this review,the pharmacology,pharmacokinetics,drug interactions of nilotinib and its safety were summerized,based on the current studies of nilotinib in clinical trials for imatinib-resistant CML and Ph＋ ALL.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2008年第21期1894-1897,共4页
Chinese Journal of New Drugs
