Optimization of Valganciclovir for Treatment of Cytomegalovirus Infection in Pediatric Liver Transplant Recipients: A Prospective Pharmacokinetic Study.

Abstract

Background: Valganciclovir (VGCV) is the first-line therapeutic agent for cytomegalovirus (CMV) infection following pediatric liver transplantation (LT). The dosage for pediatric patients is either determined by body weight (BW dose) or body surface area (BSA) and renal function (7 × BSA [m²] × creatinine clearance (CrCl) [mL/min/1.73 m²]) (BSA dose). However, the optimal dosing strategy for achieving target drug exposure for CMV treatment remains unclear.

Methods: We conducted a prospective pharmacokinetic study in pediatric LT patients. The area under the concentration-time curve (AUC_0-24) was estimated using previously reported pediatric population pharmacokinetic parameters. An AUC_0-24 of 80-120 µg·h/mL was defined as the therapeutic target. The primary endpoint was to compare the achievement rate of target AUC between BW and BSA doses. Although BW dose is the standard at our institution, a hypothetical BSA dose was estimated proportionally for comparison with BW dose.

Results: Fourteen patients with a median age of 1.1 y were included. The median VGCV dose was 15.3 mg/kg, whereas the hypothetical median BSA dose was 24.5 mg/kg. The estimated AUC_0-24 in BW and BSA dose groups were as follows: <80 µg·h/mL, 85.7% and 35.7%; 80-120 µg·h/mL, 14.3% and 42.9%; >120 µg·h/mL, 0.0% and 21.4% (P = 0.027). There was a negative correlation between AUC_0-24 and the duration of CMV viremia, indicating that higher AUC values were associated with faster viral clearance (ρ = -0.72, P = 0.003).

Conclusions: Based on our estimation, BSA dosing may be more likely to achieve the target AUC_0-24 compared with BW dosing in infant/toddler LT recipients. Higher AUC values correlated with faster viral clearance.