Abstract

Antisense oligonucleotides hold great promise as novel therapeutic agents designed to specifically and selectively inhibit the production of various disease-related gene products. For efficacy to occur, the therapeutic entity must reach the site of action in amounts sufficient to produce the desired therapeutic effect. Pharmacokinetics is defined as the study of the time course of the absorption, distribution, metabolism and elimination (ADME) of drugs. An understanding of the pharmacokinetics of antisense oligonucleotides and, in particular, the mechanisms by which oligonucleotides accumulate in tissues and in cells are critical to understanding the limitations of this technology and ultimately the development of effective antisense therapeutics. This review summarizes the known observations on the pharmacokinetics of antisense oligonucleotides with particular attention to contributions (non-clinical and clinical) published during the interval 1997 to 2000. Principles underlying the ADME of oligonucleotides are presented at the beginning of each section.