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

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 35S-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.