Ganciclovir is a nucleoside antiviral drug. Ganciclovir enters cells and is phosphorylated to a triphosphate compound, which competitively inhibits DNA polymerase and incorporates into viral DNA, thereby inhibiting DNA synthesis. Ganciclovir can be used for the treatment of cytomegalovirus retinitis in immunocompromised patients (including AIDS patients) and for the prevention of cytomegalovirus infection in organ transplant recipients[1-4].
In vitro, B lymphoblastoid cells were treated with Ganciclovir (1-20μg/ml) for 1-14 days. When the exposure duration exceeded 2 days, the dose of Ganciclovir was positively correlated with cytotoxicity, and the cytotoxic concentration significantly decreased with prolonged exposure time[5]. Microglial cells were treated with Ganciclovir (0.05–1mM) for 48 hours. In the presence or absence of LPS (100ng/ml), Ganciclovir did not significantly affect cell proliferation or viability[6].
In vivo, BALB/c mice were intraperitoneally injected daily with Ganciclovir (25–40mg/kg/day), starting from day 1 after infection with murine cytomegalovirus (MCMV) and continuing until day 7. Ganciclovir significantly reduced the occurrence of acute-phase myocarditis in mice[7]. BALB/c mice infected with MCMV on postnatal day 3 were intraperitoneally injected twice daily with Ganciclovir (10mg/kg) for 14 days. Ganciclovir significantly reduced the viral load in the temporal bones of mice, alleviated MCMV-induced sensorineural hearing loss, and partially protected against outer hair cell loss[8].
References:
[1] Crumpacker CS. Ganciclovir. N Engl J Med. 1996 Sep 5;335(10):721-9.
[2] Al-Badr AA, Ajarim TDS. Ganciclovir. Profiles Drug Subst Excip Relat Methodol. 2018;43:1-208.
[3] Ernst ME, Franey RJ. Acyclovir- and ganciclovir-induced neurotoxicity. Ann Pharmacother. 1998 Jan;32(1):111-3.
[4] McGavin JK, Goa KL. Ganciclovir: an update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients. Drugs. 2001;61(8):1153-83.
[5] Janoly-Dumenil A, Rouvet I, Bleyzac N, et al. Effect of duration and intensity of ganciclovir exposure on lymphoblastoid cell toxicity. Antivir Chem Chemother. 2009;19(6):257-62.
[6] Skripuletz T, Salinas Tejedor L, Prajeeth CK, et al. The antiviral drug ganciclovir does not inhibit microglial proliferation and activation. Sci Rep. 2015 Oct 8;5:14935.
[7] Lenzo JC, Shellam GR, Lawson CM. Ganciclovir and cidofovir treatment of cytomegalovirus-induced myocarditis in mice. Antimicrob Agents Chemother. 2001 May;45(5):1444-9.
[8] Haller TJ, Price MS, Lindsay SR, et al. Effects of ganciclovir treatment in a murine model of cytomegalovirus-induced hearing loss. Laryngoscope. 2020 Apr;130(4):1064-1069.
Ganciclovir是一种核苷类抗病毒药物。Ganciclovir进入细胞后被磷酸化为三磷酸化合物，竞争性抑制DNA多聚酶并掺入病毒DNA中从而抑制DNA合成。Ganciclovir可用于免疫缺陷患者（包括艾滋病患者）的巨细胞病毒性视网膜炎治疗和器官移植受者的巨细胞病毒感染预防[1-4]。
在体外，Ganciclovir（1-20μg/ml）处理B淋巴母细胞1-14天。当暴露时间超过2天时，Ganciclovir的剂量与细胞毒性呈正相关，同时细胞毒性浓度随暴露时间延长而显著降低[5]。Ganciclovir（0.05–1mM）处理小胶质细胞48小时。在存在或不存在LPS（100ng/ml）的情况下，Ganciclovir没有显著影响细胞增殖或活力 [6]。
在体内，Ganciclovir（25–40mg/kg/day）每日腹腔注射于BALB/c小鼠，从感染鼠巨细胞病毒（MCMV）后第1天开始，持续到第7天。Ganciclovir显著减少了小鼠急性期心肌炎的发生[7]。Ganciclovir（10mg/kg）每日两次腹腔注射于出生后第3天感染MCMV的BALB/c小鼠，持续14天。Ganciclovir显著降低了小鼠颞骨内的病毒载量，减轻了MCMV诱导的感音神经性听力损失，并部分保护了外毛细胞损失[8]。