Effect of Food on the Relative Bioavailability of Oral Ganciclovir

Abstract

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.

The Developability Classification System: Application of Biopharmaceutics Concepts to Formulation Development

“…In regard to food effects, gancyclovir is known to exhibit a small (20% increase) but significant food effect at 1000 mg,101 but in a separate study, showed a larger, more significant doubling of AUC with food at 2000 mg 102. At conventional doses acyclovir (3 × 200 mg dosed 4 h apart) shows equivalent AUCs fasted and fed,98 although a high fat meal has been shown to slightly reduce (by about 18%) the extent of oral absorption of a 400 mg dose compared to a low fat meal 103.…”

The Role of Ganciclovir in Transplantation

“…Oral absorption of ganciclovir is delayed, with a time to peak concentration T max ranging between 2 and 14 h, depending on the type of transplanted organ and the conditions under which the medication is administered [13][14][15][16] . Absorption of ganciclovir is also erratic and incomplete, with a mean bioavailability of 4.5 % ( ± 1 %) under fasting conditions [17] .…”

“…Absorption of ganciclovir is also erratic and incomplete, with a mean bioavailability of 4.5 % ( ± 1 %) under fasting conditions [17] . The rate and extent of ganciclovir absorption is greatly affected by food, particularly meals high in fat [15] . An open-label, randomized, crossover study was conducted in patients who were seropositive for both human immunodeficiency virus (HIV) and CMV.…”

Interação fármaco-nutriente: uma revisão

“…Assim, é de fundamental importância conhecer as substâncias ativas cuja velocidade de absorção e/ou quantidade são alteradas, bem como aquelas que não são afetadas pela presença de nutrientes (Toothaker & Welling, 1980). Estudos aprofundados com humanos sobre estes mecanismos têm sido realizados, com a finalidade de demonstrar mais precisamente os efeitos dos nutrientes sobre a biodisponibilidade dos fármacos (Radulovic et al, 1995;Lavelle et al, 1996). Analgésicos e antiinflamatórios, por exemplo, são com freqüência administrados com alimentos.…”