Pharmacokinetics studies of 4′-cyano-2′-deoxyguanosine, a potent inhibitor of the hepatitis B virus, in rats

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives: 4′-cyano-2′-deoxyguanosine (CdG), a novel nucleoside analogue, has a high degree of antiviral activity against the chronic hepatitis B virus (HBV). The objective of this study was to develop an analytical method for quantitatively determining CdG levels in biological samples by liquid chromatography–mass spectrometry (LC/MS) and to investigate the pharmacokinetic properties of CdG in rats after intravenous and oral administration. Methods: An analytical method using a UPLC system interfaced with a TOF-MS system was developed and validated. The pharmacokinetic properties after the intravenous and oral administration of CdG to rats were evaluated. In vivo pharmacokinetic interactions between CdG and entecavir were also investigated. Key findings: A rapid, simple and selective method for the quantification of CdG in biological samples was established using LC/MS with solid-phase extraction. In vivo pharmacokinetic studies of CdG in rats demonstrated that CdG is highly bioavailable, is rapidly absorbed from the intestinal tract, is then distributed to the liver rather than kidney and is ultimately excreted via the urine in an unchanged form. The co-administration of CdG and entecavir led to pharmacokinetic interactions with each other. Conclusions: The data generated in this study provide support for the clinical development of CdG for use in the treatment of HBV.

Original languageEnglish
Pages (from-to)723-731
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume70
Issue number6
DOIs
Publication statusPublished - 2018 Jun 1
Externally publishedYes

Keywords

  • chronic hepatitis B
  • liquid chromatography–mass spectrometry
  • nucleoside analogue
  • pharmacokinetic

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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