Pharmacokinetics oligonucleotide drugs

Levin AA, Yu RZ, Geary RS. Basic Principles of the Pharmacokinetics Of antisense Oligonucleotide drugs. In Crooke ST, ed. Antisense Drug Technology. New York Dekker, 2007. 

Considerations regarding the effective production and use of oligonucleotide drugs include stability, delivery and pharmacokinetics. 

Crooke, R.M., In vitro toxicology and pharmacokinetics of antisense oligonucleotides, Anti-Cancer Drug Design, 1991, 6, 609-646. 

Nakajima, S., Koshino, Y., Nomura, T., Yamashita, F., Agrawal, S., Takakura, Y. and Hashida, M. (2000) Intratumoral pharmacokinetics of oligonucleotides in a tissue-isolated tumor perfusion system. Antisense Nucleic Acid Drug Develop., 10, 105-110. 

Peng, B., Andrews, J., Nestorov, I., Brennan, B., Nicklin, P. and Rowland, M. (2001) Tissue distribution and physiologically based pharmacokinetics of antisense phosphorothioate oligonucleotide ISIS 1082 in rat. Antisense Nucleic Acid Drug Develop., 11, 15-27. 

Pharmacokinetic and pharmacodynamic principles are equally applicable to conventional small-molecule drugs and biotech drugs such as peptides, proteins, and oligonucleotides. Since biotech drugs are frequently identical or similar to endogenous substances, however, they often exhibit unique pharmacokinetic and pharmacodynamic properties that are different from traditional small-molecule drugs and resemble more those of endogenous macromolecules. 

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. 

J. Matson, H. Sasmor, L. Cummins, and A.A. Levin. 2003. Pharmacokinetics of a tumor necrosis factor-alpha phosphorothioate 2 -0-(2-methoxyethyl) modified antisense oligonucleotide comparison across species. Drug Metah. Dispos. 31 1419-1428. 

M. Creek, and A.A. Levin. 1997. Pharmacokinetics and metabolism in mice of a phosphorothioate oligonucleotide anti-sense inhibitor of C-raf-1 kinase expression. Drug Metab. Dispos. 25 1272-1281. 

A. Zutsi, A.A. Levin, and D.J. Kornbmst. 1997. Pharmacokinetics of a potential human cytomegalovirus therapeutic, a phosphorothioate oligonucleotide, after intravitreal injections in the rabbit. Drug Metab. Dispos. 25 921-926. 

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