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I would like the opinion of the panel on the use and clinical utility of serum ganciclovir levels when treating symptomatic cytomegalovirus (CMV) disease. Particularly in cases where CMV viremia and symptoms are difficult to control, and increased dosage is being considered (with or without the addition of foscarnet). Can serum levels be used as an approximate, indirect measure of intracellular, phosphorylated drug?
Regarding the role of serum ganciclovir as a guide to treatment, especially when symptoms are difficult to control, most clinicians do not routinely use ganciclovir levels during treatment of CMV. Instead, they use normograms to adjust the dose of ganciclovir according to kidney function. Some authors have demonstrated that recurrent CMV retinitis occurred most frequently when trough levels were below 0.6 mg/L, compared with patients without recurrence who had higher levels. Others have shown that effective prophylaxis in kidney transplant recipients was associated with higher plasma concentrations (ie, 1.0 mg/L).
Although inadequate levels may explain poor response in the management of CMV disease, we find that in most cases there are other contributing factors to explain why the patient is not improving. Seronegative transplant recipients may have numerous recurrences of CMV disease and may convert to seropositivity very late after transplantation. Once they convert and become seropositive, recurrences become less frequent. Some patients develop resistance to ganciclovir, and when a quantitative diagnostic test is used (ie, antigenemia or PCR), levels are rising during ganciclovir treatment. Viral testing for resistance to ganciclovir is available. In some cases, patients will not improve if immunosuppression levels are not decreased. These patients are most likely over-immunosuppressed. CMV disease is generally treated with intravenous ganciclovir. However, in special situations in which ganciclovir is administered orally and there is likely to be poor absorption (ie, cystic fibrosis, graft-vs-host disease of the gut), levels should be checked. In summary, although failure of treatment of CMV disease due to suboptimal levels of antiviral agents is possible, levels are not routinely monitored during treatment of CMV disease, and other possibilities to explain failure of treatment should be explored.
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