In vivo studies with phosphorothioate oligonucleotides: pharmacokinetics prologue. NLM AIDSLINE Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

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In vivo studies with phosphorothioate oligonucleotides: pharmacokinetics prologue.

Anticancer Drug Des. 1991 Dec;6(6):531-8. Unique Identifier : AIDSLINE MED/92126176
Iversen P; Department of Pharmacology, University of Nebraska Medical; Center, Omaha 68198-6260.

Abstract: Phosphorothioate oligonucleotides which contain 35S at each internucleoside linkage have been prepared and employed to evaluate the in vivo pharmacokinetics in mice, rats and rabbits. A single administration of a 27-mer complementary to the rev gene of HIV into adult male rats by either the intravenous or intraperitoneal route reveals a biphasic plasma elimination. An initial half-life of 15-25 min represents distribution out of the plasma compartment and a second half-life of 20-40 h represents elimination from the body. The second half-life is significantly longer than a variety of nucleic acids such as poly-IC and Ampligen and suggests therapy with phosphorothioate oligonucleotides should be possible and practical. Repeated daily injections of the 27-mer provides steady-state concentrations in 6-9 days, confirming the estimated long half-life from single injection studies. Finally, chronic treatment studies indicate that the phosphorothioate oligonucleotides are relatively non-toxic. Hence, pharmacokinetic considerations are not likely to be limiting factors in anti-cancer drug design with phosphorothioate oligonucleotides.
Keywords: Animal Base Sequence Human Molecular Sequence Data Oligonucleotides/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS Support, U.S. Gov't, P.H.S. Thionucleotides/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL

KWDanimalbasesequencehumanmolecularsequencedataoligonucleotides/administration&dosage/KWDpharmacokineticssupport,uKWDsKWDgov't,pKWDhKWDsKWDthionucleotides/administration&dosage/KWDpharmacokineticsjournalarticlereviewreview,tutorial
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