Whitley R J, Connell J, Markiewicz M A, Sommadossi J P
Department of Pediatrics, University of Alabama, Birmingham 35294.
Ann N Y Acad Sci. 1990;616:452-60. doi: 10.1111/j.1749-6632.1990.tb17864.x.
Two novel antiviral pharmacologic strategies were used for therapy of life- and sight-threatening cytomegalovirus (CMV) infection; these were continuous drug infusion by portable pump and individualized patient regimen. 9-(1,3-Dihydroxy-2-propoxymethyl)-guanine (DHPG), an active and recently licensed antiviral drug against cytomegalovirus infection, was administered to five immunocompromised patients with chorioretinitis (all patients), colitis (two), and pneumonitis (three). Through dosage escalation, correlations between plasma levels, toxicity (i.e., myelosuppression), and clinical benefit were ascertained for therapy of acute disease (pneumonitis) as well as long-term therapy (chorioretinitis). Resolution of viremia, pneumonitis, colitis, and chorioretinitis was accomplished with steady-state plasma levels of DHPG approximating the mean ID50 of CMV isolates. The most notable clinical benefit was survival from CMV pneumonia and stabilization of vision. Although no adverse toxicity occurred during the DHPG continuous long-term therapy, survival was limited by the underlying disease.
两种新型抗病毒药理学策略被用于治疗危及生命和视力的巨细胞病毒（CMV）感染；这两种策略分别是使用便携式泵持续输注药物以及个体化患者治疗方案。9-(1,3-二羟基-2-丙氧甲基)-鸟嘌呤（DHPG）是一种针对巨细胞病毒感染的活性且最近已获许可的抗病毒药物，被用于治疗5例免疫功能低下的患有脉络膜视网膜炎（所有患者）、结肠炎（2例）和肺炎（3例）的患者。通过剂量递增，确定了血浆水平、毒性（即骨髓抑制）与急性疾病（肺炎）以及长期治疗（脉络膜视网膜炎）的临床疗效之间的相关性。当DHPG的稳态血浆水平接近CMV分离株的平均半数感染剂量（ID50）时，病毒血症、肺炎、结肠炎和脉络膜视网膜炎得到缓解。最显著的临床疗效是从CMV肺炎中存活以及视力稳定。尽管在DHPG长期持续治疗期间未发生不良毒性反应，但患者的存活受到基础疾病的限制。
