Antisense Pharmacokinetics & Safety

In Vitro Metabolic Stabilities and Metabolism of 2'-O-(methoxyethyl) Partially Modified Phosphorothioate Antisense Oligonucleotides in Preincubated Rat or Human Whole Liver Homogenates

Baek MS, Yu RZ, Gaus H, Grundy JS, Geary RS

Oligonucleotides. 2010 Dec;20(6):309-16

Effect of Dose and Plasma Concentration on Liver Uptake and Pharmacologic Activity of a 2'-Methoxyethyl Modified Chimeric Antisense Oligonucleotide Targeting PTEN.

Geary RS, Wancewicz E, Matson J, Pearce M, Siwkowski A, Swayze E, Bennett F

Biochem Pharmacol. 2009 Aug;78(3):284-91.

Antisense Oligonucleotide Pharmacokinetics and Metabolism.

Geary RS.

Expert Opin Drug Metab Toxicol. 2009 April;5(4):381-91.

Short Antisense Oligonucleotides with Novel 2'-4' Conformationaly Restricted Nucleoside Analogues Show Improved Potency Without Increased Toxicity in Animals.

Seth PP, Siwkowski A, Allerson CR, Vasquez G, Lee S, Prakash TP, Wancewicz EV, Witchell D, Swayze EE.

J Med Chem. 2009 Jan 8;52(1):10-3

Cross-Species Pharmacokinetic Comparison from Mouse to Man of a Second-Generation Antisense Oligonucleotide, ISIS 301012, Targeting Human Apolipoprotein B-100.

Yu RZ, Kim TW, Hong A, Watanabe TA, Gaus HJ, Geary RS.

Drug Metab Dispos. 2007 Mar;35(3):460-8. Epub 2006 Dec. 15.

Absolute bioavailability of 2'-o-(2-methoxyethyl)-modified antisense oligonucleotides following intraduodenal instillation in rats.

Geary, R. S., Khatsenko, O., Bunker, K., Crooke, R., Moore, M., Burckin, T., Truong, L., Sasmor, H., and Levin, A. A.

J Pharmacol Exp Ther. 296(3):898-904, 2001.

Pharmacokinetic properties of 2'-o-(2-methoxyethyl)-modified oligonucleotide analogs in rats.

Geary, R. S., Watanabe, T. A., Truong, L., Freier, S., Lesnik, E. A., Sioufi, N. B., Sasmor, H., Manoharan, M., and Levin, A. A.

J Pharmacol Exp Ther. 296(3):890-897, 2001.

Pharmacokinetics and pharmacodynamics of an antisense phosphorothioate oligonucleotide targeting fas mrna in mice.

Yu, R. Z., Zhang, H., Geary, R. S., Graham, M., Masarjian, L., Lemonidis, K., Crooke, R., Dean, N. M., and Levin, A. A.

J Pharmacol Exp Ther. 296(2):388-395, 2001.

Toxicity of antisense oligonucleotides.

Levin, A., Henry, S., Monteith, D., and Templin, M.

Antisense Drug Technology: Principles, Strategies, and Applications (ed. Crooke, S.T.), pp. 201-267. Marcel Dekker, Inc., New York, 2001.

Clinical safety of phosphorothioate oligodeoxynucleotides.

Dorr, A., Glover, J., and Kwoh, J.

Antisense Drug Technology: Principles, Strategies, and Applications (ed. Crooke, S.T.), pp. 269-290. Marcel Dekker, Inc., New York, 2001.

Phosphorothioate oligodeoxynucleotides distribute similarly in class a scavenger receptor knockout and wild-type mice.

Butler, M., Crooke, R.M., Graham, M.J., Lemonidis, K.M., Lougheed, M., Murray, S.F., Witchell, D., Steinbrecher, U., Bennet, C.F.

J Pharmacol Exp Ther. 292(2):489-496, 2000.

Chemically modified oligonucleotides exhibit decreased immune stimulation in mice.

Henry, S., Stecker, K., Brooks, D., Monteith, D., Conklin, B., and Bennett, C. F.

J Pharmacol Exp Ther. 292(2):468-479, 2000.

In vivo distribution and metabolism of a phosphorothioate oligonucleotide within rat liver after intravenous administration.

Graham, M.J., Crooke, S. T., Monteith, D. K., Cooper, S. R., Lemonidis, K. M., Stecker, K. K., Martin, M. J., and Crooke, R. M.

J Pharmacol. Exp Ther. 286(1):447-458, 1998.

Cellular distribution of phosphorothioate oligodeoxynucleotides in normal rodent tissues.

Butler, M., Stecker, K., and Bennett, C. F.

Lab Invest. 77(4):379-388, 1997.