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Single‐Dose Pharmacokinetics of Valganciclovir in HIV‐ and CMV‐Seropositive Subjects
Author(s) -
Jung Donald,
Dorr Albert
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922008452
Subject(s) - ganciclovir , valganciclovir , pharmacokinetics , bioavailability , prodrug , pharmacology , cmax , oral administration , medicine , human cytomegalovirus , immunology , virus
As a result of the low oral bioavailability of ganciclovir, a prodrug was developed to improve the bioavailability of ganciclovir. This study was designed to investigate the fasting, single‐dose pharmacokinetics as well as the absolute and relative bioavailability of a valine ester prodrug of ganciclovir, valganciclovir, as compared to oral and intravenous ganciclovir in asymptomatic HIV+ and CMV+ subjects. In this open‐label, randomized, three‐period crossover study, 18 subjects received, in random order, single oral doses of valganciclovir 360 mg and ganciclovir 1000 mg and an intravenous infusion of ganciclovir 5 mg/kg over 1 hour. Valganciclovir was rapidly and extensively hydrolyzed to ganciclovir, resulting in significantly greater bioavailability compared to 1000 mg oral ganciclovir (60.9% vs. 5.6%, respectively). Higher peak serum concentrations were reached earlier following valganciclovir (ganciclovir [2.98 ± 0.77 μg/mL at 1.0 ± 0.3 h]) than following oral ganciclovir (0.47 ± 0.17 μg/mL and 2.2 ± 1.0 h). Mean total ganciclovir AUCs following oral ganciclovir (1000 mg) and 360 mg valganciclovir (3.8 ± 1.2 and 10.8 ± 1.9 μg‐h/mL) were less than that following a standard 5 mg/kg intravenous infusion of ganciclovir (25.1 ± 3.8 μg‐h/mL). In summary, valganciclovir is a prodrug with a favorable safety profile with enhanced bioavailability and significantly higher serum concentrations of ganciclovir than following oral administration of ganciclovir itself.