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 administration, PS-oligonucleotide clears out rapidly from the plasma and is distributed to majority of the organs. PS-oligonucleotides are bound to plasma proteins extensively. This study was aimed to determine the effect of aspirin, a commonly used drug, on pharmacokinetics of PS-oligonucleotides. In the present study, PS-oligonucleotide was administered to rats that had received aspirin by gavage. Pharmacokinetic study shows that if PS-oligonucleotide was administered following aspirin administration in rats, a) plasma pharmacokinetic parameters (t1/2alpha?, t1/2beta, AUC, etc.) had lower values, b) tissue disposition was different, and c) rate and route of elimination was affected in animals compared to rats receiving PS-oligonucleotide alone. This finding suggests that pharmacokinetics of PS-oligonucleotides can be affected with certain class of drugs, which may have direct impact on biological activity and safety.
Agrawal
S
S
Hybridon, Inc., Cambridge, MA 02139, USA.
Zhang
X
X
Cai
Q
Q
Kandimalla
E R
ER
Manning
A
A
Jiang
Z
Z
Marcel
T
T
Zhang
R
R
D000818:Animals; D019540:Area Under Curve; D001241:Aspirin / Q000494:pharmacology*; D001483:Base Sequence; D001798:Blood Proteins / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution
D001798:Blood Proteins; D013873:Thionucleotides; D001241:Aspirin