EFFECT OF ASPIRIN ON PROTEIN-BINDING AND TISSUE DISPOSITION OF OLIGONUCLEOTIDE PHOSPHOROTHIOATE IN RATS

Pharmacokinetic studies of phosphorothioate oligodeoxynucleotides (PS- oligonucleotides) in animals show that following intravenous administr ation, PS-oligonucleotide clears out rapidly from the plasma and is di stributed to majority of the organs. PS-oligonucleotides are bound to plasma proteins extensively. This study was aimed to determine the eff ect of aspirin, a commonly used drug, on pharmacokinetics of PS-oligon ucleotides. In the present study, PS-oligonucleotide was administered to rats that had received aspirin by gavage. Pharmacokinetic study sho ws that if PS-oligonucleotide was administered following aspirin admin istration in rats, a) plasma pharmacokinetic parameters (t(1/2 alpha)? , t(1/2 beta), AUC, etc.) had lower values, b) tissue disposition was different, and c) rate and route of elimination was affected in animal s compared to rats receiving PS-oligonucleotide alone. This finding su ggests that pharmacokinetics of PS oligonucleotides can be affected wi th certain class of drugs, which may have direct impact on biological activity and safety.