Geary R S, Yu R Z, Levin A A
Isis Pharmaceuticals Inc, Carlsbad, CA 92008, USA.
Curr Opin Investig Drugs. 2001 Apr;2(4):562-73.
Phosphorothioate (PS) oligodeoxynucleotides represent the class of antisense drugs most advanced in development and clinical testing. Exploitation of antisense oligonucleotide technology for development of rationally designed therapeutic drugs has presented a unique set of challenges, some of which relate to their pharmacokinetic behavior in vivo. Pharmacokinetic studies of PS oligodeoxynucleotides demonstrate that they are well absorbed from parenteral sites, rapidly distributed broadly to all peripheral tissues, do not cross the blood-brain barrier, and are eliminated primarily by slow metabolism in tissues. In general, the pharmacokinetic properties of this class of compounds appear to be largely driven by chemistry rather than sequence.
硫代磷酸酯（PS）寡脱氧核苷酸是在开发和临床试验中最先进的一类反义药物。利用反义寡核苷酸技术开发合理设计的治疗药物带来了一系列独特的挑战，其中一些与它们在体内的药代动力学行为有关。PS寡脱氧核苷酸的药代动力学研究表明，它们可从非肠道给药部位良好吸收，迅速广泛分布到所有外周组织，不穿过血脑屏障，并且主要通过组织中的缓慢代谢而消除。一般来说，这类化合物的药代动力学性质似乎在很大程度上由化学结构而非序列驱动。
