Effect of food on high-dose oral ganciclovir disposition in HIV-positive subjects

The effect of food on the steady-state pharmacokinetics of ganciclovir foll owing high-dose oral ganciclovir in HIV- and CMV-seropositive subjects was investigated in an open-label, randomized, two-treatment crossover study. O ver 2 consecutive weeks, subjects received in random order multiple oral do ses of ganciclovir 2000 mg tid for 3 consecutive days either on an "empty s tomach" (i.e., at least 2 hour before or 2 hours after a meal or snack) or within 30 minutes of finishing a meal. For the 3 days of dosing each week, the breakfast consisted of a standardized 602 calorie, high-fat (46.5) meal , while the contents of lunch, dinner, and snacks met American Dietetic Ass ociation recommendations (25%-35% fat). Serial blood samples over 24 hours were obtained on day 3 of each regimen over the first dosing interval. When ganciclovir was administered within 30 minutes following the breakfast, th ere was a mean increase of 110.6% +/- 79.0% and 114.1% +/- 81.7% in Cmax0-5 and AUC(0-5), respectively, with a prolongation of mean T-max from 1.8 to 2.7 hours. Over the total day of dosing, there was a mean increase of 47.6% +/- 12.3% and 97.2% +/- 30.9% in Cmax0-24 and AUC(0-24), respectively, and a 36.0% +/- 18.0% decrease in half-life when doses were taken following a meal as compared to when taken on an empty stomach. Since food increases th e systemic availability of ganciclovir, it is recommended that patients be instructed to take each dose of ganciclovir with food. (C) 1999 the America n College of Clinical Pharmacology.