Open AccessPharmacokinetics studies of 4′‐cyano‐2′‐deoxyguanosine, a potent inhibitor of the hepatitis B virus, in rats
Author(s) -
Hashimoto Mai,
Taguchi Kazuaki,
Ishiguro Takako,
Kohgo Satoru,
Imoto Shuhei,
Yamasaki Keishi,
Mitsuya Hiroaki,
Otagiri Masaki
Publication year - 2018
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12897
Subject(s) - pharmacokinetics , entecavir , in vivo , pharmacology , oral administration , bioavailability , chemistry , deoxyguanosine , hepatitis b virus , nucleoside , nucleoside analogue , urine , chromatography , medicine , virus , virology , lamivudine , biochemistry , biology , dna , microbiology and biotechnology
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 .