Single-dose pharmacokinetics of valganciclovir in HIV- and CMV-seropositive subjects

As a result of the low oral bioavailability of ganciclovir, a prodrug was d eveloped to improve the bioavailability of ganciclovir. This study was desi gned to investigate the fasting, single-dose pharmacokinetics as well as th e absolute and relative bioavailability of a valine ester prodrug of gancic lovir, valganciclovir, as compared to oral and intravenous ganciclovir in a symptomatic HIV+ and CMV+ subjects. In this open-label, randomized, three-p eriod crossover study, 18 subjects received, in random order, single oral d oses of valganciclovir 360 mg and ganciclovir 1000 mg and an intravenous in fusion of ganciclovir 5 mg/kg over 1 hour. Valganciclovir was rapidly and e xtensively hydrolyzed to ganciclovir, resulting in significantly greater bi oavailability compared to 1000 mg oral ganciclovir (60.9% vs. 5.6%, respect ively). Higher peak serum concentrations were reached earlier following val ganciclovir (ganciclovir [2.98 +/- 0.77 mu g/mL at 1.0 +/- 0.3 h]) than fol lowing oral ganciclovir (0.47 +/- 0.17 mu g/mL and 2.2 +/- 1.0 h). Mean tot al ganciclovir AUCs following oral ganciclovir (1000 mg) and 360 mg valganc iclovir (3.8 +/- 1.2 and 10.8 +/- 1.9 mu g-h/mL) were less than that follow ing a standard 5 mg/kg intravenous infusion of ganciclovir (25.1 +/- 3.8 mu g-h/mL). In summary, valganciclovir is a prodrug with a favorable safety p rofile with enhanced bioavailability and significantly higher serum concent rations of ganciclovir than following oral administration of ganciclovir it self: Journal of Clinical Pharmacology, 1999;39:800-804 (C) 1999 the Americ an College of Clinical pharmacology.