Goal: To validate oral vatgancictovir (VGC) in the
prophylaxis of CMV infection in Lung (Lu) and
Liver (L) recipients and in the treatment of CMV
infection/disease in solid organ transplant recipients,
using pharmacokinetic and pharmacodynamic
studies in comparison with i/v gancicLovir (GCV).
Methods: patients undergoing organ transpLantation
donor or recipient CMV-seropositive receiving
VGC prophylaxis for a period of 3 months
(D+/R- Lung recipients, 6 months) were enroLLed.
Heart (H), Lu, and L recipients received 900mg
VGC q.d., adjusted to kidney (K) function. No K recipients
received more than 450mg of VGC q.d.
GCV trough (Ctrough) and peak (Cpeak = 3 hours after
drug administration) LeveLs, and CMV DNA were
measured at 7, 30, and 60 days post-transpLant
(prophyLactic study). Patients who developed CMV
infection/disease after stopping prophylaxis were
treated with VGC (1800mg per day adjusted to
K function and GCV blood LeveLs). GCV trough and
peak LeveLs, and CMV DNA were measured weekly
for the first 3 weeks and biweekly thereafter, until
therapy cessation (therapeutic study). PLasma concentration
of GCV is measured by HPLC.
Results: In the first 8 prophyLaxed patients (6 K,
and 1 L and 1 H transplant recipient) of 450mg
VGC q.d., the average GCV concentration was
0.5±0.3 mg/t at trough, and 3.9±l.0mg/t 3 hours
after administration. Inter-patient variability was
substantiaL, especiaLLy for Ctrough (63% of total
variance), which correlated with the patient's estimated
gtomerutar filtration rate (r square = 42%).
No CMV DNA was detected during VGC prophy-
Laxis. Two patients (1 H and 1 L) were treated
for Late CMV disease. Average GCV Cpeak were
8.9±2.3 mg/L and 4.6±0.5 rag/L, and GCV Ctrough
were 2.0±0.9 mg/t and 1.6±0.2 mg/t respectively
in each patient during induction phase. VGC treatment
afforded a decrease in CMV DNA from 5.2
and 4.4 Log copies/10E6 cettutes at week 0, to 3.9
and 3.0 at week 1, and 3.3 and 2.1 at week 3,
respectively.