钴胺素代谢及其不同形式的临床应用

Cobalamin metabolism and the clinical application in its different forms

钴胺素,即维生素B 12,是自然界中结构最复杂的维生素,也是人体必需的维生素之一,在体内作为生物辅酶参与同型半胱氨酸代谢和甲基丙二酰辅酶A与琥珀酰辅酶A的转化等多项生理活动。人类作为高等生物,无法自行合成钴胺素,需要通过饮食或药物来补充人体所需的钴胺素。目前,用于治疗的钴胺素形式多样,常见形式有氰钴胺(普通维生素B 12)、羟钴胺、甲钴胺和腺苷钴胺。不同形式的钴胺素结构相似,理化性质相近,但在吸收、分布、代谢和消除等药代动力学方面存在一定差异性,临床应用和治疗效果也有所不同。其中,氰钴胺和羟钴胺在欧美地区应用甚广,甲钴胺在亚洲应用较多,腺苷钴胺已在国内批准上市,但世界范围内应用不多。氰钴胺和甲钴胺主要用于治疗周围神经病变和钴胺素缺乏引起的疾病,羟钴胺曾批准作为氰化物的解毒剂,近年来在甲基丙二酸血症的治疗方面发挥了一定作用。现从4种钴胺素的化学结构、理化性质、药代动力学特征及临床应用等进行比较和区分,为临床合理用药提供参考,以免发生混淆。

Cobalamin,also known as Vitamin B12,is the most complex vitamin in nature,and also one of essential vitamins in human body,which involved in many physiological activities,including homocysteine metabolism and translation of methylmalonyl-CoA to succinyl-CoA as a biological coenzyme.As a higher organism,human cannot synthesize cobalamin by themselves,so cobalamin needs to be supplemented by diet or medicine.At present,there are various forms of cobalamin,including cyanocobalamin(a common form of Vitamin B12),hydroxylcobalamin,mecoba-lamin and 5′-adenosylcobalamin.These different forms of cobalamin are similar in structures and physiochemical pro-perties,but have some differences in the pharmacokinetics of absorption,distribution,metabolism and elimination,as well as clinical application and therapeutic efficacy.Among them,cyanocobalamin and hydroxycobalamin are widely used in Europe and the United States.Mecobalamin is more commonly used in Asia.5′-adenosylcobalamin has been approved in China,but less widely used in the world.Cyanocobalamin and mecobalamin are mainly used for the treatment of diseases caused by peripheral neuropathy and cobalamin deficiency.Hydroxycobalamin has been approved as an antidote to cyanide and has shown some potential in the treatment of methylmalonic acidemia in recent years.Now,the chemical structures,physiochemical properties,pharmacokinetic characteristics and clinical applications of the four cobalamins were compared and distinguished,so as to provide references for clinicians in clinical rational drug use and to avoid confusion.