In vitro antihepadnaviral activities of combinations of penciclovir, lamivudine, and adefovir

Citation
D. Colledge et al., In vitro antihepadnaviral activities of combinations of penciclovir, lamivudine, and adefovir, ANTIM AG CH, 44(3), 2000, pp. 551-560
Citations number
41
Categorie Soggetti
Microbiology
Journal title
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN journal
00664804 → ACNP
Volume
44
Issue
3
Year of publication
2000
Pages
551 - 560
Database
ISI
SICI code
0066-4804(200003)44:3<551:IVAAOC>2.0.ZU;2-E
Abstract
Penciclovir {9-[2-hydroxy-1-(hydroxymethyl)-ethoxymethyl]guanine [PCV]}, la mivudine ([-]-beta-L-2',3'-dideoxy-3' -thiacytidine [3TC]), and adefovir (9 -[2-phosphonylmethoxyethyl]-adenine [PMEA]) are potent inhibitors of hepati tis B virus (HBV) replication. Lamivudine has recently received approval fo r clinical use against chronic human HBV infection, and both PCV and PMEA h ave undergone clinical trials against HBV in their respective prodrug forms {famciclovir and adefovir dipivoxil [bis-(POM)-PMEA]}. Since multidrug com binations are likely to be used to control HBV infection, investigation of potential interactions between PCV, 3TC, and PMEA is important. Primary duc k hepatocyte cultures which were either acutely or congenitally infected wi th the duck hepatitis B virus (DHBV) were used to investigate in vitro inte ractions between PCV, 3TC, and PMEA. Here we show that the anti-DHBV effect s of all the combinations containing PCV, 3TC, and PMEA are greater than th at of each of the individual components and that their combined activities are approximately additive or synergistic. These results may underestimate the potential in vivo usefulness of PMEA containing combinations, since the re is evidence that PMEA has immunomodulatory activity and, at least in the duck model of chronic HBV infection, is capable of inhibiting DHBV replica tion in cells other than hepatocytes, the latter being unaffected by treatm ent with either PCV or 3TC. Further investigation of the antiviral activiti es of these drug combinations is therefore required, particularly since eac h of the component drugs is already in clinical use.