Evaluation of anti-hepatitis B virus (HBV) drugs using the HBV transgenic mouse: application of the semiquantitative polymerase chain reaction (PCR) for serum HBV DNA to monitor the drug efficacy.
For evaluation of anti-hepatitis B virus (HBV) drugs, we have employed the HBV transgenic mouse in which virion-like particles can be assayed in the serum. Bispivaloyloxymethyl-9-(2-phosphonylmethoxyethyl)-adenine [bis (POM) PMEA] 100 mg/kg/day, 2',3'-dideoxy-3'-thiacytidine [(+-)-BCH189] 200 mg/kg/day and a placebo were orally administered to mice twice a day for 14 days. Anti-viral effects were monitored by checking the levels of serum HBV DNA by the semiquantitative polymerase chain reaction, HBsAg and HBeAg by enzyme immunoassay, and replicative intermediates in the liver by Southern blotting. As expected, decrease from the 10(0.5) to 10(3) copies of HBV DNA per microl of sera detected before the treatment to the undetectable level was evident for all five animals treated with bis(POM) PMEA 100 mg/kg/day. However (+-)-BCH189 200 mg/kg/day, which is known to act as the inhibitor of reverse transcriptase for HBV or HIV in vivo and in vitro, did not suppress HBV DNA levels in the transgenic mouse. Thus, we were able to detect the effects of anti-HBV drugs semi-quantitatively, and confirm differences in drug efficacy.
Kajino
K
K
Department of Experimental Pathology, Cancer Institute, 1-37-1 Kami-Ikebukuro, Toshimaku, Tokyo, 170, Japan.
Kamiya
N
N
Yuasa
S
S
Takahara
T
T
Sakurai
J
J
Yamamura
K i
Ki
Hino
O
O
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000097:blood*; D016903:Drug Monitoring; D006509:Hepatitis B / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction / Q000379:methods*; D014771:Virion / Q000235:genetics / Q000302:isolation & purification; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; C089823:bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine; D019259:Lamivudine; D000225:Adenine