Srinivas Nuggehally R
Zydus Research Centre, Ahmedabad, Gujarat, 382210, India.
Eur J Drug Metab Pharmacokinet. 2018 Aug;43(4):373-382. doi: 10.1007/s13318-018-0466-x.
Pimasertib belongs to the growing family of mitogen activated protein kinase (MEK1/2) inhibitors undergoing clinical development for various cancer indications. Since the MEK inhibition in several cell signalling transduction cascades within tumours was considered therapeutically beneficial, number of clinical investigations of pimasertib have been reported. Despite being orally bioavailable in cancer patients, pimasertib undergoes faster clearance with a short elimination half-life. In addition, due to occurrence of toxicity, the development of pimasertib appears to be stalled. Case studies are provided on the possible utilization of pimasertib in combination therapies with other approved drugs. Based on the review, it appeared that there was the need to identify the optimal dose and the dosing regimen of pimasertib to provide a balance between safety and efficacy when combined with approved therapies.
匹马替尼属于正在为各种癌症适应症进行临床开发的丝裂原活化蛋白激酶(MEK1/2)抑制剂这一不断壮大的家族。由于抑制肿瘤内多个细胞信号转导级联反应中的MEK被认为具有治疗益处,已有多项关于匹马替尼的临床研究报告。尽管匹马替尼在癌症患者中口服生物利用度良好,但它的清除速度较快,消除半衰期较短。此外,由于毒性的出现,匹马替尼的开发似乎已陷入停滞。文中提供了关于匹马替尼与其他已获批药物联合治疗的可能应用的案例研究。基于该综述,似乎有必要确定匹马替尼的最佳剂量和给药方案,以便在与已获批疗法联合使用时在安全性和有效性之间取得平衡。