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The steady-state pharmacokinetics of oral ganciclovir in the fasting versus fed state were studied in 20 patients infected with human immunodeficiency virus and with a seropositive test result for cytomegalovirus in a two-way crossover study. Patients received oral ganciclovir at a dose of 1000 mg every 8 hours for 8 days. On days 4 and 8, subjects were randomly assigned to receive the morning dose either after an overnight fast or after a standardized 602-calorie, high-fat (46.5%) breakfast. Serial blood samples were obtained over the 8-hour morning dose interval. The mean time to maximum concentration (tmax) was increased from 1.8 hours in the fasting state to 3.0 hours in the fed state. Mean maximum serum concentration (Cmax) and area under the concentration-time curve from time 0 to 8 hours (AUC0-8) of ganciclovir were significantly higher in the fed state than after an overnight fast. Because food could potentially increase the bioavailability of oral ganciclovir, patients should be instructed to take each dose of oral ganciclovir with food.