{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:43:51Z","timestamp":1778636631118,"version":"3.51.4"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Health and Labor Sciences Research Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>4\u2032-cyano-2\u2032-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\u2013mass spectrometry (LC\/MS) and to investigate the pharmacokinetic properties of CdG in rats after intravenous and oral administration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The data generated in this study provide support for the clinical development of CdG for use in the treatment of HBV.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.12897","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T09:02:47Z","timestamp":1520845367000},"page":"723-731","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetics studies of 4\u2032-cyano-2\u2032-deoxyguanosine, a potent inhibitor of the hepatitis B virus, in rats"],"prefix":"10.1093","volume":"70","author":[{"given":"Mai","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , Kumamoto,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuaki","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , Kumamoto,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , Kumamoto,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Kohgo","sequence":"additional","affiliation":[{"name":"Center for Clinical Sciences, National Center for Global Health and Medicine , Shinjuku,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"Imoto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , Kumamoto,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keishi","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , Kumamoto,","place":["Japan"]},{"name":"DDS Research Institutes, Sojo University , Kumamoto,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Mitsuya","sequence":"additional","affiliation":[{"name":"Center for Clinical Sciences, National Center for Global Health and Medicine , Shinjuku,","place":["Japan"]},{"name":"Department of Infectious Diseases and Hematology, Kumamoto University School of Medicine , Kumamoto,","place":["Japan"]},{"name":"Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6244-3825","authenticated-orcid":false,"given":"Masaki","family":"Otagiri","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University , Kumamoto,","place":["Japan"]},{"name":"DDS Research Institutes, Sojo University , Kumamoto,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,6,1]]},"reference":[{"key":"2024103012325172500_jphp12897-cit-0001","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/j.vaccine.2011.12.116","article-title":"Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and 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