Maribavir: a novel antiviral agent with activity against cytomegalovirus.
OBJECTIVE
To review the pharmacology, pharmacokinetics, efficacy, and safety of maribavir, a novel antiviral agent in the benzimidazole drug class.


METHODS
Articles were identified through searches of MEDLINE (January 1998-July 2008). Abstracts from recent scientific meetings and the manufacturer were also included.


METHODS
All English-language in vitro and in vivo studies and abstracts evaluating maribavir were reviewed and considered for inclusion. All human studies were included.


RESULTS
Maribavir has significant activity against both human cytomegalovirus (CMV) and Epstein-Barr virus, but not other herpesviruses. Unlike ganciclovir, which needs to be phosphorylated by UL 97 kinase to become an active inhibitor of DNA polymerase, maribavir directly inhibits UL 97 kinase. UL 97 kinase is an early viral gene product involved in viral DNA elongation, DNA packaging, and egress or shedding of capsids from viral nuclei. Maribavir has also been found to be effective against ganciclovir-resistant CMV strains. Maribavir differs from current CMV antiviral agents in its adverse event profile. Maribavir is not associated with nephrotoxicity or hematologic toxicities, but has been associated with taste disturbances. In February 2007, maribavir was granted Food and Drug Administration orphan drug status for prevention of CMV viremia and diseases in at-risk populations. Maribavir Phase 2 trials in stem-cell transplant recipients have been completed, and there are ongoing Phase 3 trials in stem-cell and organ transplant recipients.


CONCLUSIONS
Maribavir may be an option for treatment of ganciclovir-resistant CMV infections. Its bioavailability is greater than that of oral ganciclovir, but less than that of valganciclovir. No differences in pharmacokinetics were seen in renally impaired patients, although dialysis-dependent patients were not evaluated. Maribavir is not associated with hematologic toxicities; however, the high prevalence of taste disturbances may limit its tolerability.
Trofe
Jennifer
J
Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. jennifer.trofe@uphs.upenn.edu
Pote
Lindsey
L
Wade
Erin
E
Blumberg
Emily
E
Bloom
Roy D
RD
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D024882:Drug Resistance, Viral; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy; D004854:Herpesvirus 4, Human / Q000187:drug effects; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects / Q000378:metabolism; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
D000998:Antiviral Agents; D001562:Benzimidazoles; D017853:Phosphotransferases (Alcohol Group Acceptor); D012263:Ribonucleosides; C075365:ganciclovir kinase; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole