Evaluation of SQ 34,514: pharmacokinetics and efficacy in experimental herpesvirus infections in mice.
The new antiviral nucleoside SQ 34,514 [(1R-1 alpha, 2 beta, 3 alpha)-2-amino-9- [2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one], the active R isomer of racemic SQ 33,054 (cyclobut-G), was evaluated for efficacy in the treatment of herpesvirus infections in mice. SQ 34,514 was orally efficacious in a herpes simplex virus type 1 (HSV-1) systemic infection, an intracerebral HSV-2 infection, a vaginally induced HSV-2 infection in ovariectomized mice, and in a systemic murine cytomegalovirus infection. SQ 34,514 compared favorably with acyclovir and ganciclovir in the treatment of these experimental infections. In mice, SQ 34,514 had an oral bioavailability of 80% based on urinary excretion. SQ 34,514 may have potential value in the therapy of HSV and cytomegalovirus infections in humans.
Braitman
A
A
Department of Microbiology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Swerdel
M R
MR
Olsen
S J
SJ
Tuomari
A V
AV
Lynch
J S
JS
Blue
B
B
Michalik
T
T
Field
A K
AK
Bonner
D P
DP
Clark
J M
JM
D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001927:Brain Diseases / Q000188:drug therapy / Q000382:microbiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006561:Herpes Simplex / Q000188:drug therapy*; D051379:Mice; D014627:Vaginitis / Q000188:drug therapy / Q000382:microbiology; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D006147:Guanine; C063638:lobucavir