New prophylactic treatment strategy for cytomegalovirus disease.
The pharmacology, pharmacokinetics, safety, and efficacy of valganciclovir, an oral prodrug for ganciclovir, used to prevent cytomegalovirus (CMV) disease in solid organ transplant recipients are described. Valganciclovir was developed to overcome the disadvantages associated with ganciclovir, which include low oral bioavailability, limited efficacy because of the development of viral resistance, and the need for frequent administration, which can adversely affect patient adherence. Valganciclovir is rapidly converted to ganciclovir; systemic exposure to the parent drug is low and short in duration. The oral bioavailability of ganciclovir from valganciclovir is 10 times higher than that from the original ganciclovir formulation. Food increases the oral bioavailability of valganciclovir. In a four-way, randomized, crossover pharmacokinetic study of 28 liver transplant recipients, single doses of valganciclovir 900 mg and intravenous ganciclovir 5 mg/kg resulted in a similar ganciclovir systemic exposure. The systemic exposure was proportionately lower with a single 450-mg dose of valganciclovir but similar to that of oral ganciclovir 3 g administered in three divided doses. In the recent multicenter, randomized, double-blind, double-dummy PV16000 trial in 364 solid organ transplant recipients at high risk for CMV disease (i.e., CMV-negative recipients of CMV-positive donor organs), valganciclovir 900 mg once daily was as effective in preventing CMV-disease as oral ganciclovir 1 g three times daily. Resistance was reported with ganciclovir but not with valganciclovir. Both drugs were well tolerated.
Lake
Kathleen D
KD
University of Michigan Medical School, Department of Medicine and Surgery, 3914 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA. kdlake@umich.edu
D000284:Administration, Oral; D019072:Antibiotic Prophylaxis; D000998:Antiviral Agents / Q000627:therapeutic use*; D001682:Biological Availability; D003586:Cytomegalovirus Infections / Q000150:complications / Q000517:prevention & control*; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D009894:Opportunistic Infections / Q000150:complications / Q000517:prevention & control / Q000821:virology; D016032:Randomized Controlled Trials as Topic; D000077562:Valganciclovir
D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir