ArticleAntimicrobial agents and chemotherapy2012
A pharmacodynamic model of ganciclovir antiviral effect and toxicity for lymphoblastoid cells suggests a new dosing regimen to treat cytomegalovirus infection.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review of the Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Ganciclovir/Valganciclovir in Allogeneic Haematopoietic Stem Cell Transplant Patients.Clinical pharmacokinetics · 2021Pooled it
- Distribution of ganciclovir in the porcine central nervous system.Antimicrobial agents and chemotherapy · 2025Article
- Effect of host telomerase inhibition on human cytomegalovirus.Journal of virology · 2025Article
- Characterization of Human Cytomegalovirus (HCMV) Long Non-Coding RNA1.2 During Lytic Replication.Viruses · 2025Article
- Lactobacilli-Derived Postmetabolites Are Broad-Spectrum Inhibitors of Herpes Viruses In Vitro.International journal of molecular sciences · 2024Article
- Photodynamic Inactivation of Human Herpes Virus In Vitro with Ga(III) and Zn(II) Phthalocyanines.Viruses · 2024Article
- Population Pharmacokinetics of Ganciclovir in Allogeneic Hematopoietic Stem Cell Transplant Patients.Antimicrobial agents and chemotherapy · 2023Observational
- Hypoxia-directed tumor targeting of CRISPR-Cas9 and HSV-TK suicide gene therapy using lipid nanoparticles.Molecular therapy. Methods & clinical development · 2022Article
- Standard ganciclovir dosing results in slow decline of cytomegalovirus viral loads.The Journal of antimicrobial chemotherapy · 2022Article
- Therapeutic Drug Monitoring of Ganciclovir: Where Are We?Therapeutic drug monitoring · 2022Review
- Cyclodextrins in Antiviral Therapeutics and Vaccines.Pharmaceutics · 2021Review
- Small bowel perforation secondary to CMV-positive terminal ileitis postrenal transplant.BMJ case reports · 2019Article
- Article
- Effect of a Histone Demethylase Inhibitor on Equine Herpesvirus-1 ActivityFrontiers in veterinary science · 2018Article
- New strategies against drug resistance to herpes simplex virus.International journal of oral science · 2016Review
- Letermovir Treatment of Human Cytomegalovirus Infection Antiinfective Agent.Drugs of the future · 2013Article
- Extensive Longitudinal Transverse Myelitis Associated With CSF Epstein-Barr Virus Infection: A Case Report.Child neurology openArticle
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In bone marrow transplantation, the efficacy of ganciclovir in cytomegalovirus (CMV) disease treatment or prophylaxis remains partial. Because its hematological toxicity is dose limiting, optimization of the dosing schedule is required to increase its therapeutic index. The goal of our study was to describe the influence of the ganciclovir concentration and duration of exposure on cell survival and antiviral efficacy. The study was carried out in vitro on cultures of lymphoblastoid cells infected or not with the CMV AD169 reference strain and exposed to ganciclovir at different concentrations for 1, 2, 7, or 14 days. The data were analyzed by a mathematical model that allowed a quantitative characterization of ganciclovir pharmacodynamics and its variability. Simulations of the model were undertaken to determine the optimal concentration profile for maximizing the ganciclovir therapeutic index. Ganciclovir had very little toxic and antiviral effect, even at 20 mg liter(-1), when the duration of exposure was ≤ 7 days. A biologically significant effect was observed only with a 14-day exposure. Complete inhibition of viral replication was obtained at 20 mg liter(-1). The utility function, assuming equal weights for antiviral effect and toxicity, showed that maximal utility was reached around 10 mg liter(-1). The optimal ganciclovir concentration profile consisted of maintaining the concentration at 20 mg liter(-1) at the intervals 0 to 2 days and 7.58 to 9.58 days and a null concentration at other times. This optimal profile could be obtained by intravenous (i.v.) ganciclovir at 10 mg/kg of body weight twice daily (b.i.d.) at days 1, 2, 8.5, and 9.5 in stem cell transplant patients with normal renal function.
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