Evaluation of Ganciclovir for Cytomegalovirus Disease

Abstract

Cytomegalovirus (CMV) infections are a common cause of morbidity and mortality in immunosuppressed patients. Ganciclovir is an acyclic deoxyguanosine analog structurally similar to acyclovir but with superior activity against CMV. The median ganciclovir concentration required to inhibit viral replication by 50 percent is 2.15 mumol versus 72 mumol for acyclovir. Pharmacokinetic properties of ganciclovir include biexponential decay with a terminal half-life of 2.5 hours, tissue uptake, cerebrospinal fluid penetration, and renal dependence for elimination. CMV treatment approaches have commonly used dosages of 3-15 mg/kg/d. In uncontrolled trials, the response rate of CMV retinitis is approximately 80 percent. The overall response rate for CMV pneumonitis has been approximately 50 percent. However, AIDS (acquired immunodeficiency syndrome) and other immunosuppressed patients appear to respond more favorably (approximately 70 percent) than do marrow transplant recipients. Relapse is common once ganciclovir is stopped and maintenance therapy may be required for sustained benefit. Neutropenia appears to be the drug-limiting adverse reaction. Although the development of ganciclovir-resistant CMV, risk factors for neutropenia, and alternative administration strategies all need further study, ganciclovir appears to have a role in the treatment of cytomegalovirus disease.