Shukla Jaya, Dinda Amit Kumar, Srivastava Abhay Krishna, Srivastava Kamna, Mittal Bhagwant Rai, Bandopadhyaya Guru Pad
Department of Nuclear Medicine and PET, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
World J Nucl Med. 2016 Jan-Apr;15(1):7-11. doi: 10.4103/1450-1147.167594.
Tamoxifen is the most prescribed anticancer oral drug for increasing overall survival and decreasing recurrence and the risk of contralateral disease. However, some side effects, such as endometrial and liver tumors, thromboembolic disorders, and drug resistance, are associated with long-term tamoxifen treatment. We assessed the hematologic and organ toxicity after oral administration of three different doses of nanotamoxifen formulations. We also performed biodistribution studies of Technetium-99m ((99m)Tc)-nanotamoxifen after intravenous administration. The results demonstrated that nanotamoxifen was well-tolerated, with no adverse effect on biochemical parameters of blood and at the cellular level. Nitric oxide (NO) levels indicated no free radical formation. Oral nanotamoxifen is well-tolerated, with no hepatic or renal toxicity. Intravenous nanotamoxifen has potential to escape the liver, and is known for producing the harmful metabolite 4-hydroxytamoxifen (4OH-tamoxifen), which can cause uterine cancer.
他莫昔芬是最常被处方的抗癌口服药物，可提高总生存率、降低复发率和对侧疾病风险。然而，长期使用他莫昔芬治疗会产生一些副作用，如子宫内膜和肝脏肿瘤、血栓栓塞性疾病以及耐药性。我们评估了口服三种不同剂量的纳米他莫昔芬制剂后的血液学和器官毒性。我们还进行了静脉注射99m锝（(99m)Tc）标记的纳米他莫昔芬的生物分布研究。结果表明，纳米他莫昔芬耐受性良好，对血液生化参数和细胞水平均无不良影响。一氧化氮（NO）水平表明没有自由基形成。口服纳米他莫昔芬耐受性良好，无肝毒性或肾毒性。静脉注射纳米他莫昔芬有可能避开肝脏，并且已知会产生有害代谢物4-羟基他莫昔芬（4OH-他莫昔芬），可导致子宫癌。
