Steady-state relative bioavailability of three oral ganciclovir dosage regimens delivering 6,000 mg/day in patients with human immunodeficiency virus

This study was designed to determine the steady-state relative bioavailability of ganciclovir after three dosage regimens designed to deliver 6,000 mg/day. The study design was an open-label, randomized, three-treatment crossover design in which 22 human immunodeficiency virus (HIV) and cytomegalovirus (CMV) seropositive patients received in random order multiple oral doses of ganciclovir 1,000 mg six times a day, 1,500 mg four times a day, and 2,000 mg three times a day. Blood samples were obtained on day 3 of each oral regimen over a 24-hour time interval. Mean steady-state average serum concentrations of ganciclovir were greater than 1.0 microgram/mL, which exceeds the median in vitro inhibitory concentration (IC50) of most CMV isolates (0.5-1.0 microgram/mL). All three regimens resulted in values for area under the concentration-time curve from 0 to 24 hours (AUC0-24) that were comparable to those seen after maintenance ganciclovir intravenous infusions of 5 mg/kg/day. The 1,000 mg six times daily regimen resulted in an AUC0-24 that was significantly higher than that of the 1,500 mg four times daily or the 2,000 mg three times daily regimens, although the differences were less than 12.5%.