Pharmacokinetic properties of a novel inosine analog, 40-cyano-20-deoxyinosine, after oral administration in rats

Mai Hashimoto, Kazuaki Taguchi, Takako Ishiguro, Satoru Kohgo, Shuhei Imoto, Keishi Yamasaki, Hiroaki Mitsuya, Masaki Otagiri

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Abstract

40-cyano-20-deoxyinosine (SK14-061a), a novel nucleoside analog based on inosine, has antiviral activity against the human immunodeficiency virus type 1 that has the ability to acquire resistance against many types of reverse transcriptase inhibitors based on nucleosides. The aim of this study was to investigate the pharmacokinetics studies after its oral administration to rats. For this purpose, we first developed and validated an analytical method for quantitatively determining SK14-061a levels in biological samples by a UPLC system interfaced with a TOF-MS system. A rapid, simple and selective method for the quantification of SK14-061a in biological samples was established using liquid chromatography mass spectrometry (LC-MS) with solid phase extraction. The pharmacokinetic properties of SK14-061a in rats after oral administration were then evaluated using this LC-MS method. SK14-061a was found to be relatively highly bioavailable, is rapidly absorbed from the intestinal tract, and is then mainly distributed to the liver and then ultimately excreted via the urine in an unchanged form. Furthermore, the simultaneous administration of SK14-061a with the nucleoside analog, entecavir, led to a significant alteration in the pharmacokinetics of SK14-061a. These results suggest that the SK14-061a has favorable pharmacokinetic properties with a high bioavailability with the potential for use in oral pharmaceutical formulations, but drug-drug interactions should also be considered.

Original languageEnglish
Article numbere0198636.
JournalPLoS One
Volume13
Issue number6
DOIs
Publication statusPublished - 2018 Jun 1
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hashimoto, M., Taguchi, K., Ishiguro, T., Kohgo, S., Imoto, S., Yamasaki, K., Mitsuya, H., & Otagiri, M. (2018). Pharmacokinetic properties of a novel inosine analog, 40-cyano-20-deoxyinosine, after oral administration in rats. PLoS One, 13(6), [e0198636.]. https://doi.org/10.1371/journal.pone.0198636