Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients.
BACKGROUND
A randomized, double-blind study was conducted to evaluate the pharmacokinetics of ganciclovir following oral administration of ganciclovir or valganciclovir for prophylaxis of cytomegalovirus (CMV) disease in solid organ transplant recipients (n = 240/372).


METHODS
The correlations between individual exposure to ganciclovir during prophylaxis, with CMV viremia incidence during and after treatment, CMV disease up to 12 months posttransplant, and hematological toxicity were assessed.


RESULTS
Mean daily areas under the curve (AUCs) of ganciclovir from valganciclovir and oral ganciclovir were 46.3 +/- 15.2 and 28.0 +/- 10.9 microg.h/ml (mean +/- SD), respectively. Viremia was suppressed during prophylaxis when exposure to ganciclovir was 40-50 microg.h/ml, AUCs typical of those achieved in valganciclovir-treated patients. The development of viremia 1 month after ending prophylaxis was also reduced with higher ganciclovir AUC (median predicted incidence, 20% and 10% at AUCs of 33 and 50 microg h/ml, respectively). The development of CMV disease within 1 year of transplant was 17.6% and independent of prophylactic exposure to ganciclovir. There was only a weak tendency to increased neutropenia and leukopenia with higher ganciclovir exposure.


CONCLUSIONS
The greater systemic exposure to ganciclovir delivered by valganciclovir was associated with delayed development of viremia. There was only a weak association between AUC and hematological toxicity.
Wiltshire
Hugh
H
Roche Products, Welwyn Garden City, Herts, UK.
Paya
Carlos V
CV
Pescovitz
Mark D
MD
Humar
Atul
A
Dominguez
Edward
E
Washburn
Kenneth
K
Blumberg
Emily
E
Alexander
Barbara
B
Freeman
Richard
R
Heaton
Nigel
N
Zuideveld
Klaas P
KP
D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001827:Body Height; D001835:Body Weight; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D011183:Postoperative Complications / Q000821:virology*; D000077562:Valganciclovir; D019562:Viral Load; D014766:Viremia / Q000453:epidemiology
D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir