Oral ganciclovir and pharmacokinetics of valganciclovir in liver transplant recipients.
The pivotal trial demonstrating efficacy of oral ganciclovir in preventing cytomegalovirus (CMV) disease following organ transplantation was conducted in liver transplant recipients, in whom the rate of CMV disease was reduced from 19% to 5%. Pharmacokinetic analyses have indicated that oral ganciclovir dosing should be adjusted, based on renal function, to achieve adequate drug levels. With normal renal function, 1 g t.i.d. of oral ganciclovir is required to achieve such adequate systemic levels. Children require proportionally more drug than adults do: in the range 600-800 mg/m2 to achieve adequate dosing. The development of an oral prodrug, valganciclovir, may help to obviate some of the drug exposure issues raised with oral ganciclovir. The ester linkage of the amino acid valine to ganciclovir results in ten-fold higher bioavailability of ganciclovir: 450 mg of valganciclovir given once daily produces drug exposure similar to that achieved with 3 g of oral ganciclovir; 900 mg of valganciclovir given once daily produces drug exposures equivalent to that of 5 mg/kg of IV ganciclovir. This drug may improve prophylactic efficacy in the high-risk CMV seropositive donor/seronegative negative recipient transplant groups and may also allow treatment of established CMV disease with an oral formulation.
Pescovitz
M D
MD
Surgery and Microbiology/Immunology, Indiana University, Indianapolis 46202, USA. mpescov@iupui.edu
D000284:Administration, Oral; D000328:Adult; D002648:Child; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D016031:Liver Transplantation; D011183:Postoperative Complications / Q000517:prevention & control / Q000821:virology*; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077562:Valganciclovir
D011355:Prodrugs; D000077562:Valganciclovir; D015774:Ganciclovir