Unexpectedly high inter- and intrapatient variability of ganciclovir levels in children.

Few studies report Ganciclovir or Valganciclovir levels in children. Single-center, retrospective study of all available Ganciclovir levels in transplanted children. Ganciclovir monitoring was performed as previously described [G. Filler (1998); Pediatric Nephrology, 12, 6]. For the normalization of dosing to GFR and target trough levels, we assumed first-order kinetics. We analyzed 57 Ganciclovir levels in 20 children (mean age 8.6 +/- 5.5 yr) treated with intravenous or oral Ganciclovir or oral Valganciclovir. Ganciclovir levels were drawn after IV therapy (n = 9), during oral Ganciclovir (n = 5), or during oral Valganciclovir (n = 15). Oral bioavailability of Valganciclovir was 42.0 +/- 21.8%. The dose-normalized intrapatient Valganciclovir variability was 83%. Mean GFR was 92 +/- 22 mL/min/1.73 m(2). Mean Ganciclovir concentration at last available measurement was 0.60 +/- 0.09 mg/L. While target trough Ganciclovir levels have not been established, possibly subtherapeutic Ganciclovir levels <0.5 mg/L on recommended IV doses were found in eight patients. This subset of patients was significantly younger (4.5 +/- 3.1 vs. 11.4 +/- 5.0 yr). Levels <0.5 mg/L were found in 24/57 instances and 10 patients subsequently had their dose increased. The last Valganciclovir dose adjusted to a GFR of 100 mL/min/1.73 m(2) was 842 +/- 323 mg/m(2)/day. A high proportion of patients had low Ganciclovir levels both on intravenous and oral therapy. The oral bioavailability of Valganciclovir was 42%. Our data suggest substantial inter- and intrapatient variability of Ganciclovir levels after pediatric renal transplantation and may support the need for pharmacokinetic monitoring of Ganciclovir and Valganciclovir therapy for the prevention and treatment of CMV disease after pediatric transplantation. It is currently unclear what target trough level would be most suitable.