PMID- 32879218
OWN - NLM
STAT- MEDLINE
DCOM- 20210616
LR  - 20220312
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Print)
IS  - 0918-6158 (Linking)
VI  - 43
IP  - 9
DP  - 2020
TI  - Pharmacokinetic Properties of Orally Administered 4'-Cyano-2'-deoxyguanosine, a 
      Novel Nucleoside Analog Inhibitor of the Hepatitis B Virus, in Viral Liver Injury 
      Model Rats.
PG  - 1426-1429
LID - 10.1248/bpb.b20-00372 [doi]
AB  - A nucleoside analog, 4'-cyano-2'-deoxyguanosine (CdG), which was developed as an 
      inhibitor of the chronic hepatitis B virus (HBV), exhibited a superior antiviral 
      activity against both wild-type and drugs-resistant HBV to marketed nucleoside 
      analogs. In addition to previous pharmacokinetic studies of CdG in healthy rats, 
      this study reports on an evaluation of the pharmacokinetic characteristics of CdG 
      in a rat model of viral liver injury (VLI) induced by treatment with concanavalin 
      A. Following an intravenous administration of CdG at a dose of 1 mg/kg, the 
      plasma concentration profile of CdG in VLI model rats was found to be similar to 
      that of healthy rats with no significant difference in kinetic parameters. 
      However, when CdG was orally administered at a dose of 1 mg/kg, the maximum blood 
      concentration was much lower in VLI model rats than in healthy rats. 
      Interestingly, the amount of residual food in the stomachs in VLI model rats was 
      significantly larger than that in healthy rats, indicating that the adsorption of 
      CdG in the gastrointestinal tract was inhibited in the presence of food as well 
      as other marketed nucleoside analogs. As observed in healthy rats, CdG was 
      largely distributed to the liver compared to the kidney in the VLI model. These 
      results suggest that liver pathology has only a minor effect on the 
      pharmacokinetic properties of CdG, but the influence of food on CdG absorption 
      needs to be considered.
FAU - Hashimoto, Mai
AU  - Hashimoto M
AD  - Faculty of Pharmaceutical Sciences, Sojo University.
FAU - Taguchi, Kazuaki
AU  - Taguchi K
AD  - Faculty of Pharmacy, Keio University.
FAU - Imoto, Shuhei
AU  - Imoto S
AD  - Faculty of Pharmaceutical Sciences, Sojo University.
FAU - Yamasaki, Keishi
AU  - Yamasaki K
AD  - Faculty of Pharmaceutical Sciences, Sojo University.
AD  - DDS Research Institutes, Sojo University.
FAU - Mitsuya, Hiroaki
AU  - Mitsuya H
AD  - Center for Clinical Sciences, National Center for Global Health and Medicine.
AD  - Department of Infectious Diseases and Hematology, Kumamoto University School of 
      Medicine.
AD  - Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National 
      Cancer Institute, National Institutes of Health.
FAU - Otagiri, Masaki
AU  - Otagiri M
AD  - Faculty of Pharmaceutical Sciences, Sojo University.
AD  - DDS Research Institutes, Sojo University.
LA  - eng
GR  - ZIA BC011486/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (4'-cyano-2'-deoxyguanosine)
RN  - 0 (Antiviral Agents)
RN  - 11028-71-0 (Concanavalin A)
RN  - G9481N71RO (Deoxyguanosine)
SB  - IM
MH  - Administration, Intravenous
MH  - Animals
MH  - Antiviral Agents/administration & dosage/*pharmacokinetics
MH  - Chemical and Drug Induced Liver Injury/blood/etiology/*pathology
MH  - Concanavalin A/administration & dosage/toxicity
MH  - Deoxyguanosine/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Food-Drug Interactions
MH  - Gastrointestinal Absorption
MH  - Hepatitis B, Chronic/*drug therapy/pathology
MH  - Humans
MH  - Liver/drug effects/*pathology/virology
MH  - Male
MH  - Rats
PMC - PMC8916165
MID - NIHMS1780970
OTO - NOTNLM
OT  - acute liver injury
OT  - disposition
OT  - food-drug interaction
OT  - hepatitis B
OT  - nucleoside analog
COIS- Conflict of Interest The authors declare no conflict of interest.
EDAT- 2020/09/04 06:00
MHDA- 2021/06/17 06:00
PMCR- 2022/03/11
CRDT- 2020/09/04 06:00
PHST- 2020/09/04 06:00 [entrez]
PHST- 2020/09/04 06:00 [pubmed]
PHST- 2021/06/17 06:00 [medline]
PHST- 2022/03/11 00:00 [pmc-release]
AID - 10.1248/bpb.b20-00372 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2020;43(9):1426-1429. doi: 10.1248/bpb.b20-00372.