Evaluation of valganciclovir pharmacokinetics in lung transplant recipients.

Background: Valganciclovir is commonly used for cytomegalovirus prevention after lung transplantation. The pharmacokinetic profile of valganciclovir in lung transplant patients has not been well described or linked to efficacy and safety.

Methods: This prospective, randomized, crossover study determined the steady-state pharmacokinetic profile of 2 different doses of valganciclovir in lung transplant recipients and compared these profiles with intravenous ganciclovir.

Results: Ten patients were evaluated. Patients were 56.8 ± 3.4 years old and had a mean creatinine clearance of 69 ± 9 ml/min. Oral bioavailability of ganciclovir after administration of valganciclovir was 59%, and mean half-life was 3.73 ± 1.15 hours. The maximal concentration after intravenous 5 mg/kg ganciclovir was significantly higher than after 450 mg valganciclovir (8.37 ± 3.03 mg/liter vs. 5.3 ± 2.09 mg/liter, respectively; p = 0.02) and similar to 900 mg valganciclovir (7.93 ± 3.97 mg/liter; p = 0.78). A higher area under the curve at 0-24 hours (AUC(0-24)) was found with 900 mg valganciclovir compared with intravenous 5 mg/kg/day ganciclovir (47.8 ± 19.7 vs 32.9 ± 10.8 mg · hour/liter, respectively; p = 0.049). The AUC(0-24) for 450 mg valganciclovir twice daily was 45.5 ± 22.9 mg · hour/liter.

Conclusion: Valganciclovir at 900 mg/day resulted in the equivalent of a mean daily dose of 7.7 mg/kg intravenous ganciclovir. Higher systemic ganciclovir exposures occurred after 900 mg/day valganciclovir compared with intravenous 5 mg/kg/day ganciclovir. Valganciclovir therapeutic drug monitoring may be warranted in select lung transplant patients to avoid increased toxicity.