Establishing pharmacokinetic bioequivalence of valganciclovir oral solution versus the tablet formulation.

摘要

Dosing with valganciclovir tablets may not be appropriate in some patients, such as those on hemodialysis or children. A "tutti-frutti" flavored oral valganciclovir solution has been developed to provide flexibility in dosage needed to accommodate these patients. An adult, multicenter, open-label randomized trial was conducted to establish bioequivalence between valganciclovir oral solution and valganciclovir tablets. Pharmacokinetic profiles and safety of the oral solution versus the tablet formulation were determined in 23 renal transplant recipients with estimated creatinine clearance>or=60 mL/min who had been receiving cytomegalovirus prophylaxis with valganciclovir for >or=4 days prior to the administration of the study drug. Patients received two doses of 900 mg valganciclovir either by tablet or oral solution in random order once daily over 6 days. Plasma concentrations of ganciclovir were assessed on days 2, 4, and 6 predose and at 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, and 12 hours after the dose. Maximum mean plasma concentrations (Cmax) were 6.73 microg/mL and 6.39 microg/mL for the valganciclovir tablet and oral solution, respectively, with identical mean AUC0-24 of 51.2 microg.h/mL. For both the AUC0-24 and Cmax ratio, the 90% Cl of the mean ratios of the oral solution relative to the tablet formulation lies within the acceptance region (80% to 125%) required by the US Food and Drug Administration and European Agency for the Evaluation of Medicinal Products. With the demonstration of bioequivalence and no differences in the incidence of adverse effects, it will be possible to interchangeably use the oral formulation.