chapter  7
34 Pages

Basic Principles of the Pharmacokinetics of Antisense Oligonucleotide Drugs

WithArthur A. Levin, Rosie Z. Yu, Richard S. Geary

References ......................................................................................................................................211

7.1 INTRODUCTION

The pharmacokinetic properties of antisense oligonucleotides (ASOs) are best understood in the context of their physical and chemical properties. Charge, molecular weight, and amphipathic nature of the ASOs all influence the pharmacokinetics of phosphorothioate ASOs. This review will concentrate on how chemical modifications, particularly, the phosphorothioate modification and the 2-methoxyethyl (MOE) modification, of second-generation ASOs improve the pharmacokinetic properties.