OBJECTIVES To delineate the pharmacokinetic profile of the oral capsule formulation of ganciclovir, and determine whether oral ganciclovir has any pharmacokinetics interactions with zidovudine, didanosine or probenecid. MEASUREMENTS Serum and urine concentrations of ganciclovir, zidovudine and didanosine were measured. From these concentrations, standard pharmacokinetic parameters such as peak concentration, area under the curve (AUC), elimination half-life and renal clearance were determined. RESULTS The bioavailability of oral ganciclovir averages 6-9%. Inter- and intrasubject variability of AUC is low (coefficient of variation 21.8 and 12.6%, respectively). The steady-state AUCs achieved with oral ganciclovir (1000 mg three times daily or 500 mg six times daily) are approximately 70% of the AUC achieved with the daily maintenance dose of intravenous ganciclovir (5 mg/kg). Serum concentrations of ganciclovir are 20% higher when the oral formulation is administered with a high fat meal than when taken following an overnight fast. Serum concentrations of didanosine (200 mg every 12 h) are approximately doubled when taken in combination with oral ganciclovir (1000 mg every 8 h). CONCLUSIONS Although bioavailability of the oral formulation of ganciclovir is low, the serum concentrations are predictable, with low inter- and intrasubject variability in peak concentrations and AUC. The two oral regimens studied (500 mg six times daily or 1000 mg three times daily) have comparable bioavailability. Food has a beneficial effect of increasing serum concentrations. There is a potentially important pharmacokinetic interaction between oral ganciclovir and didanosine.