title: Absolute bioavailability and dose proportionality of oral ganciclovir after ascending multiple doses in human immunodeficiency virus (HIV)-positive patients.
abstract: This study was designed to determine the bioavailability and dose linearity and proportionality of ganciclovir after multiple oral administrations of 3,000 mg to 6,000 mg per day. In an open-label, randomized, four-treatment crossover design, 24 patients seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) received in random order multiple oral doses of ganciclovir 1,000 mg every 3 hours (six times a day), 1,000 mg four times a day, and 1,000 mg three times a day and a single 5-mg/kg intravenous infusion (over 1 hour) of ganciclovir. Blood samples for pharmacokinetic determinations were obtained on day 3 of each oral regimen and on the day of the intravenous infusion over a 24-hour time interval. Mean steady-state average serum concentrations of ganciclovir were 0.54, 0.79, and 0.99 microgram/mL, respectively, with the 3, 4, and 6 g/day oral regimens. The steady-state area under the concentration-time curve (AUC0-24) for the 6,000 mg/day oral regimen approached that of the single-dose intravenous regimen. There was a proportional increase in AUC0-24 between the 3 and 4 g/day dosage regimens, but not between the 4 and 6 g/day regimens. This suggests nonlinear absorption of ganciclovir at higher dosages, although the departure from proportionality was less than 11%.
authors: Roche Global Development, Palo Alto, California, USA.
authors: D
authors: D
authors: Jung
authors: K
authors: K
authors: Griffy
authors: R
authors: R
authors: Wong
authors: W
authors: W
authors: Colburn
authors: J
authors: J
authors: Hulse
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D015774:Ganciclovir / Q000493:pharmacokinetics*; D006679:HIV Seropositivity / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir