Isis Pharmaceuticals, Carlsbad, CA 92010, USA.
Br J Clin Pharmacol. 2013 Aug;76(2):269-76. doi: 10.1111/j.1365-2125.2012.04469.x.
Mipomersen is a second generation antisense oligonucleotide that targets apolipoprotein B. It has been studied thoroughly in clinical trials (more than 800 subjects), including four randomized double-blind placebo controlled phase 3 studies involving 391 patients, and is in registration for the treatment of severe hypercholesterolaemia. The pharmacokinetic and pharmacodynamic properties of mipomersen are well characterized. Mipomersen is rapidly and extensively absorbed after subcutaneous administration and has an elimination half-life of approximately 30 days across species. It is cleared by nuclease metabolism and renal excretion of the metabolites. Mipomersen reduces all apolipoprotein B containing atherogenic particles and displays dose dependent reductions between 50-400 mg week⁻¹ , both as a single agent and in the presence of maximal lipid lowering therapy. No drug-drug interactions have been identified. Mipomersen is a representative of second generation antisense drugs, all of which have similar properties, and is thus representative of the behaviour of the class of drugs.
米泊美生是一种第二代反义寡核苷酸，靶向载脂蛋白 B。它已在临床试验中进行了深入研究（超过 800 名受试者），包括四项涉及 391 名患者的随机、双盲、安慰剂对照的 3 期研究，并且正在注册用于治疗严重高胆固醇血症。米泊美生的药代动力学和药效学特性已得到很好的描述。米泊美生在皮下给药后迅速广泛吸收，在所有物种中的消除半衰期约为 30 天。它通过核酸酶代谢和代谢物的肾脏排泄清除。米泊美生降低所有载脂蛋白 B 中含有的动脉粥样硬化颗粒，并显示出剂量依赖性降低，每周 50-400 毫克，无论是作为单一药物还是在最大程度降低脂质治疗的情况下。尚未发现药物相互作用。米泊美生是第二代反义药物的代表，所有这些药物都具有相似的特性，因此代表了该类药物的行为。
