Phosphorothioate oligonucleotides pharmacokinetic properties

D.K. Monteith, and A.A. Levin. 1997. Antisense oligonucleotide inhibitors for the treatment of cancer 1. Pharmacokinetic properties of phosphorothioate oligodeoxynucleotides. Anti-Cancer Drug Design 12 383-393. 

Leeds, J.M., and R.S. Geary. 1998. Pharmacokinetic properties of phosphorothioate oligonucleotides in humans. In ... 

In conclusion, phosphorothioate oligonucleotides may interact with a wide range of proteins through several types of mechanisms. These interactions may influence the pharmacokinetic, pharmacologic, and toxicologic properties of these molecules. They may also complicate studies on the mechanism of action of these drugs, and may obscure an antisense activity. For example, phosphorothio-... 

Phosphorothioate oligonucleotides have perhaps outperformed many expectations. They display attractive parenteral pharmacokinetic properties. They have produced potent systemic effects in a number of animal models and, in many experiments, the antisense mechanism has been directly demonstrated as the hoped-for selectivity. Further, these compounds appear to display satisfactory therapeutic indices for many indications. 

Henry SP, Templin MV, Gillett N, et al. Correlation of toxicity and pharmacokinetic properties of a phosphorothioate oligonucleotide designed to inhibit ICAM-1. Toxicol Pathol 1999 27 95-100. 

Geary RS, Yu RZ, Siwkowski A. Pharmacokinetic/pharmacodynamic properties of phosphorothioate 2 -0-(2-methoxyethyl) modified antisense oligonucleotides in animals and man. In Crooke ST, ed. Antisense Drug Technology. New York Dekker, 2007. 

---