Pharmacokinetics and tissue distribution of a peptide nucleic acid after intravenous administration

Beth M. McMahon, Dennis Mays, James Lipsky, Jennifer A. Stewart, Abdul Fauq, Elliott Richelson

Research output: Contribution to journalArticle

64 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)65-70
Number of pages6
JournalAntisense and Nucleic Acid Drug Development
Volume12
Issue number2
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

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