title: Pharmacokinetics and tissue distribution of a peptide nucleic acid after intravenous administration.
abstract: Peptide nucleic acids (PNAs) are DNA analogs that hybridize to complementary nucleic sequences with high affinity and stability. In our previous work, we showed that a PNA complementary to a 12-base pair (bp) sequence of the coding region of the rat neurotensin receptor (rNTR1) mRNA is effective in significantly blocking a rat's central responses to neurotensin (NT), even when the PNA is injected intraperitoneally (i.p.). Using a novel gel shift detection assay to detect PNA, we have now used this same PNA sequence to derive its pharmacokinetic variables and its tissue distribution in the rat. The PNA has a distribution half-life of 3 +/- 3 minutes and an elimination half-life of 17 +/- 3 minutes. The total plasma clearance and volume of distribution of this PNA were 3.4 +/- 0.9 ml/min x kg and 60 +/- 30 ml/kg. Two hours after dosing, the PNA was found at detectable but low levels in all organs examined-in order of decreasing concentration: kidney, liver, heart, brain, and spleen. Approximately 90% of the PNA dose was recovered as unchanged parent compound in the urine 24 hours after administration.
authors.affiliation: Laboratory of Neuropsychopharmacology, Mayo Foundation for Medical and Educational Research, Jacksonville, FL 32224, USA. mcmahon.beth@mayo.edu
authors.forename: Beth M
authors.initials: BM
authors.lastname: McMahon
authors.forename: Dennis
authors.initials: D
authors.lastname: Mays
authors.forename: James
authors.initials: J
authors.lastname: Lipsky
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Stewart
authors.forename: Abdul
authors.initials: A
authors.lastname: Fauq
authors.forename: Elliott
authors.initials: E
authors.lastname: Richelson
mesh_terms: D000818:Animals; D001483:Base Sequence; D007275:Injections, Intravenous; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000235:genetics; D014018:Tissue Distribution
chemical_list: D020319:Oligodeoxyribonucleotides, Antisense; D020135:Peptide Nucleic Acids; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor