STEADY-STATE RELATIVE BIOAVAILABILITY OF 3 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 bioavai lability of ganciclovir after three dosage regimens designed to delive r 6,000 mg/day. The study design was an open-label, randomized, three- treatment crossover design in which 22 human immunodeficiency virus (H IV) and cytomegalovirus (CMV) seropositive patients received in random order multiple oral doses of ganciclovir 2,000 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 inter val. Mean steady-state average serum concentrations of ganciclovir wer e greater than 1.0 mu g/mL, which exceeds the median in vitro inhibito ry concentration (IC50) of most CMV isolates (0.5-1.0 mu g/mL). AIL th ree regimens resulted in values for area under the concentration-time curve from 0 to 24 hours (AUC(0-24)) that were comparable to those see n after maintenance ganciclovir intravenous infusions of 5 mg/kg/day. The 2,000 mg six times daily regimen resulted in an AUC(0-24) that was significantly higher than that of the 1,500 mg four times daily or th e 2,000 mg three times daily regimens, although the differences were l ess than 12.5%. (C) 1998 The American College of Clinical Pharmacology .