title: Dosing of intravenous ganciclovir for the prophylaxis and treatment of cytomegalovirus infection in solid organ transplant recipients.
abstract: BACKGROUND
  The optimal regimen for the prevention and treatment of cytomegalovirus (CMV) disease in solid organ transplant recipients remains to be defined, particularly for patients with abnormal or changing renal function.
  
  
  METHODS
  A prospective trial was conducted in patients receiving i.v. ganciclovir using a standardized dosing nomogram that corrects for renal function. Steady state peak (P) and trough (T) serum levels were determined by high-performance liquid chromatography and correlated with therapeutic outcomes and toxicities attributable to ganciclovir.
  
  
  RESULTS
  Over the study period, 44 individuals received ganciclovir prophylaxis (5 mg(kg/day) and 25 patients were treated (5 mg/kd q12 hr) for symptomatic CMV disease. Ganciclovir levels (microg/ml+/-SD) achieved in prophylaxis were P: 7.98+/-3.34, T: 3.03+/-2.63; and in treatment were P: 9.00+/-3.72, T: 2.65+/-1.82. Despite corrections for renal dysfunction, undialyzed patients with serum creatinine >3.0 mg/dl had trough levels in excess of the population mean (T: range 3-8 microg/ml). Failure of prophylaxis (disease) or therapy (relapse) occurred in 14 patients; 8 of these were at risk for primary infection (donor CMV seropositive, recipient seronegative, P<0.01). Patients at greatest risk for relapse after treatment of CMV disease were liver transplant recipients, patients with ganciclovir-resistant viral isolates, and renal patients with six antigen MHC donor-recipient mismatches.
  
  
  CONCLUSIONS
  This trial demonstrates the efficacy of a nomogram for ganciclovir dosing during renal dysfunction; reduced doses can be used for prophylaxis for undialyzed patients with renal dysfunction (1.25 mg/kg/day for Cr > or =3.0, 1.25 mg/kg QOD for Cr > or =5.0). Some groups of transplant recipients may require more intensive anti-CMV regimens.
authors.affiliation: Transplant Infectious Disease Program, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Fishman
authors.forename: M T
authors.initials: MT
authors.lastname: Doran
authors.forename: S A
authors.initials: SA
authors.lastname: Volpicelli
authors.forename: A B
authors.initials: AB
authors.lastname: Cosimi
authors.forename: J G
authors.initials: JG
authors.lastname: Flood
authors.forename: R H
authors.initials: RH
authors.lastname: Rubin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000517:prevention & control*; D015774:Ganciclovir / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D016377:Organ Transplantation / Q000009:adverse effects*; D011446:Prospective Studies; D014184:Transplantation, Homologous
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir