Naslov
Absorption, tissue distribution and in vivo stability in rats of a hybrid antisense oligonucleotide following oral administration

Autori
Agrawal, Sudhir ; Zhang, Xueshu ; Zhao, Hui ; Lu, Zhihong ; Yan, Jieming ; Tamburin, Jeffrey M. ; Cai, Hungying ; Diasio, Robert B. ; Habuš, Ivan ; Jiang, Zhiwei ; Iyer, Radhakrishnan P. ; Yu, D. ; Zhang, R.

Izvornik
Biochemical Pharmacology (0006-2952) 50 (1995), 4; 571-576

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
oligodeoxynucleotide phosphorothioate ; 2'-O-methyloligoribonucleotide phosphorothioates

Sažetak
In vivo stability and oral bioavailability of an oligodeoxynucleotide phosphorothioate containing segments of 2'-O-methyloligoribonucleotide phosphorothioates at both the 3'- and 5'-ends (hybrid oligonucleotide) were studied. A 25-mer S-35-labeled hybrid oligonucleotide was administered to rats by gavage at a dose of 50 mg/kg body weight. HPLC analysis revealed that this hybrid oligonucleotide was stable in the gastrointestinal tract for up to 6 hr following oral administration. Radioactivity associated with the hybrid oligonucleotide was detectable in portal venous plasma, systemic plasma, various tissues, and urine. Intact hybrid oligonucleotide was detected, by HPLC analysis, in portal venous plasma, systemic plasma, and various tissues. The majority of the radioactivity in urine was associated with degradative products with lower molecular weights, but the intact form was also detected. In summary, the hybrid oligonucleotide was absorbed intact through the gastrointestinal tract, indicating the possibility of oral administration of oligonucleotides, a finding that may be important in the development of antisense oligonucleotides as therapeutic agents.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA