Debs R J, Montgomery A B, Brunette E N, DeBruin M, Shanley J D
Cancer Research Institute, University of California, San Francisco Medical Center 94143.
J Infect Dis. 1988 Feb;157(2):327-31. doi: 10.1093/infdis/157.2.327.
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.
巨细胞病毒（CMV）肺炎在骨髓移植受者和艾滋病患者中会导致显著的发病率和死亡率。9-（1,3-二羟基-2-丙氧甲基）鸟嘌呤（更昔洛韦）和膦甲酸（PFA）在人类感染中表现出对CMV的活性，尽管经常会出现CMV复发和全身药物毒性。我们研究了雾化给药抗病毒药物对鼠巨细胞病毒（MCMV）感染的疗效。动物经鼻内接种MCMV，并接受口服更昔洛韦治疗；雾化更昔洛韦、PFA或利巴韦林治疗；或缓冲液治疗。通过蚀斑测定法对肺和唾液腺匀浆中的MCMV进行定量。口服更昔洛韦（每天200mg/kg）使两种组织中的MCMV滴度降低超过95%。雾化更昔洛韦，每天100mg/kg和200mg/kg，分别使肺中MCMV滴度降低93%和97%。雾化PFA，每天20mg/kg和200mg/kg，分别使肺中MCMV滴度降低60%和68%。雾化更昔洛韦和PFA对唾液腺中MCMV复制的抑制作用明显小于口服这两种药物中的任何一种。我们的结果表明，雾化给药抗病毒药物可以有效且选择性地抑制肺中MCMV的复制。
