Ganciclovir

Ganciclovir (DHPG) is a potent antiviral drug used to treatment of cytomegalovirus (CMV) infections [1].

Ganciclovir (DHPG) is a nucleoside analogue and has shown the activity against viral thymidine kinase (tk) in the Herpesviridae family, including human cytomegalovirus and herpes simplex virus types I and II as well as Epstein-Barr virus. In addition, Ganciclovir has been reported to inhibit the proliferation of uninfected cells, most significantly of bone marrow cells, because of the function of inhibiting viral replication. Apart from these, Ganciclovir has been revealed to reduce the activation of microglial in wild-type C57BL/6 mice and inhibit proliferation of microglial in wild-type FvB mice [1].

References:
[1] Ding Z1, Mathur V, Ho PP, James ML, Lucin KM, Hoehne A, Alabsi H, Gambhir SS, Steinman L, Luo J, Wyss-Coray T. Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation. J Exp Med. 2014 Feb 10; 211(2):189-98.

Combined environmental risk assessment for the antiviral pharmaceuticals ganciclovir and valganciclovir in Europe.[Pubmed:28198039]

Environ Toxicol Chem. 2017 Aug;36(8):2205-2216.

Potential environmental risks of the old antiviral pharmaceuticals Ganciclovir (GCV) and valGanciclovir (VGCV) were reassessed based on new environmental fate and chronic ecotoxicity tests and on actual use data for Europe. ValGanciclovir is hydrolyzed to GCV by intestinal and hepatic esterases, and hence the new environmental tests only refer to GCV. A sorption study showed that GCV will not sorb significantly, excluding the soil as a relevant environmental compartment. Despite earlier data suggesting nondegradability, a new water/sediment fate test showed GCV to be primarily and ultimately degraded and to be nonpersistent. The chronic ecotoxicity tests with algae and daphnids resulted in no inhibition at the highest tested concentrations, whereas a fish partial life cycle test, selected in view of mammalian mutagenicity and reprotoxicity data, showed effects on growth of the young fish, but not on gametogenesis, fertilization, embryogenesis, or teratogenicity. Predicted environmental concentrations were derived based on actual per capita use data for European countries for 2004 to 2014, and the highest was selected for the risk assessment. A comparison of predicted environmental concentrations with predicted no-effect concentrations shows no significant risk for wastewater treatment, surface waters, groundwater, or sediment. In addition, potential risks to (semi)aquatic top predators or to human consumers of water and fish are exceedingly low. Environ Toxicol Chem 2017;36:2205-2216. (c) 2017 The Author. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

[Intravitreal ganciclovir as an additional therapy option in acute retinal necrosis].[Pubmed:28105484]

Ophthalmologe. 2017 Sep;114(9):838-842.

Acute retinal necrosis (ARN) is a rare viral inflammatory disease, characterized by uveitis, retinal vasculitis, and necrosis in the late stages. Therapeutic management is based on the clinical findings. The positive outcome in our patient (VA 0.6) indicates that, beside the management of retinal detachment and lens opacification, additional intravitreal injections of 2 mg Ganciclovir may achieve better results than systemic/topical antiviral application alone.

Risk Factors and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infection in Solid Organ Transplant Recipients.[Pubmed:28369203]

Clin Infect Dis. 2017 Jul 1;65(1):57-63.

Background: Ganciclovir-resistant (ganR) cytomegalovirus (CMV) is an emerging and important problem in solid organ transplant (SOT) recipients. Only through direct comparison of ganR- and Ganciclovir-sensitive (ganS) CMV infection can risk factors and outcomes attributable specifically to Ganciclovir resistance appropriately be determined. Methods: We performed a retrospective, case-control (1:3) study of SOT recipients with genotypically confirmed ganR-CMV (n = 37) and ganS-CMV infection (n = 109), matched by donor/recipient CMV serostatus, year and organ transplanted, and clinical manifestation. We used chi2 (categorical) and Mann-Whitney (continuous) tests to determine predisposing factors and morbidity attributable to resistance, and Kaplan-Meier plots to analyze survival differences. Results: The rate of ganR-CMV was 1% (37/3467) overall and 4.1% (32/777) among CMV donor-positive, recipient-negative patients, and was stable over the study period. GanR-CMV was associated with increased prior exposure to Ganciclovir (median, 153 vs 91 days, P < .001). Eighteen percent (3/17) of lung transplant recipients with ganR-CMV had received <6 weeks of prior Ganciclovir (current guideline-recommended resistance testing threshold), and all non-lung recipients had received >/=90 days (median, 160 [range, 90-284 days]) prior to diagnosis of ganR-CMV. GanR-CMV was associated with higher mortality (11% vs 1%, P = .004), fewer days alive and nonhospitalized (73 vs 81, P = .039), and decreased renal function (42% vs 19%, P = .008) by 3 months after diagnosis. Conclusions: GanR-CMV is associated with longer prior antiviral duration and higher attributable morbidity and mortality than ganS-CMV. Upcoming revised CMV guidelines should incorporate organ transplant-specific thresholds of prior drug exposure to guide rational ganR-CMV testing in SOT recipients. Improved strategies for prevention and treatment of ganR-CMV are warranted.

Ganciclovir is a potent herpes simplex virus (HSV)inhibitor, including cytomegalovirus (CMV), with an IC50 of 5.2 μM for feline herpesvirus type-1 (FHV-1).

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