Aerosol administration of antiviral agents to treat lung infection due to murine cytomegalovirus.
Cytomegalovirus (CMV) pneumonia causes significant morbidity and mortality in bone marrow transplant recipients and in patients with AIDS. 9-(1,3-Dihydroxy-2-propoxymethyl) guanine (ganciclovir) and phosphonoformic acid (PFA) demonstrate activity against CMV in human infections, although recurrent CMV and systemic drug toxicity frequently develop. We examined the efficacy of aerosol administration of antiviral agents against murine CMV (MCMV) infection. Animals were inoculated with MCMV intranasally and were treated with oral ganciclovir; with aerosolized ganciclovir, PFA, or ribavirin; or with buffer. MCMV in lung and salivary gland homogenates was quantified by plaque assay. Oral ganciclovir (200 mg/kg per day) reduced titers of MCMV in both tissues by greater than 95%. Aerosolized ganciclovir, 100 and 200 mg/kg per day, reduced lung titers of MCMV by 93% and 97%, respectively. Aerosolized PFA, 20 and 200 mg/kg per day, reduced lung titers of MCMV by 60% and 68%, respectively. Aerosolized ganciclovir and PFA inhibited replication of MCMV in salivary glands substantially less than did oral administration of either agent. Our results suggest that aerosol administration of antiviral agents can potently and selectively inhibit replication of MCMV in the lung.
Debs
R J
RJ
Cancer Research Institute, University of California, San Francisco Medical Center 94143.
Montgomery
A B
AB
Brunette
E N
EN
DeBruin
M
M
Shanley
J D
JD
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D017245:Foscarnet; D015774:Ganciclovir; D051379:Mice; D008807:Mice, Inbred BALB C; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D011024:Pneumonia, Viral / Q000188:drug therapy*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use
D000336:Aerosols; D000998:Antiviral Agents; D017245:Foscarnet; D012254:Ribavirin; D010746:Phosphonoacetic Acid; D015774:Ganciclovir; D000212:Acyclovir