Plasma- and serum-protein binding of antisense oligodeoxynucleotide phosphorothioates in experimental animals and humans (Meeting abstract).

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Plasma- and serum-protein binding of antisense oligodeoxynucleotide phosphorothioates in experimental animals and humans (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A2451 1995. Unique Identifier : AIDSLINE ICDB/95610225
Zhang X; Lu Z; Diasio RB; Jiang Z; Tan W; Agrawal S; Zhang R; Dept. of Pharmacol. and Toxicol., Univ. of Alabama, Birmingham,; AL 35294

Abstract: The use of antisense oligonucleotides targeted to mRNA represents an attempt at specific, genetically based therapy. In continuation of our studies in developing antisense oligonucleotides as therapeutic agents for AIDS, we have designed several antisense oligodeoxynucleotide phosphorothioates that have been shown to have significant anti-HIV effects. Pharmacokinetics of these oligonucleotides have recently been determined in rats. In the present study, the properties of plasma- and serum-binding of 4 oligodeoxynucleotide phosphorothioates were examined in humans, rats, rabbits, and guinea pigs. Pooled plasma or serum mixed with 35S- or 14C-labeled oligodeoxynucleotide phosphorothioates were incubated for 1 hr at 37 C and then loaded onto Ultrafree filtration tubes followed by centrifugation at 34 C to determine protein binding ratio of these oligonucleotides. Concentration-dependent protein binding ratio was demonstrated with all the tested oligonucleotides for all the species, with significant differences observed among these oligonucleotides and by species. Albumin was identified to be the major component responsible for protein binding of these oligonucleotides among other proteins. Protein binding may be one of the major factors affecting pharmacokinetics and tissue disposition of these oligonucleotides .

Keywords: Animal Antineoplastic Agents/CHEMISTRY/*PHARMACOKINETICS Antiviral Agents/CHEMISTRY/*PHARMACOKINETICS Human HIV/DRUG EFFECTS Metabolic Clearance Rate Oligonucleotides, Antisense/CHEMISTRY/*PHARMACOKINETICS Protein Binding ABSTRACT
950930
M9591320

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