Effect of food on high-dose oral ganciclovir disposition in HIV-positive subjects.
The effect of food on the steady-state pharmacokinetics of ganciclovir following high-dose oral ganciclovir in HIV- and CMV-seropositive subjects was investigated in an open-label, randomized, two-treatment crossover study. Over 2 consecutive weeks, subjects received in random order multiple oral doses of ganciclovir 2,000 mg tid for 3 consecutive days either on an "empty stomach " (i.e., at least 1 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 Association 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, there was a mean increase of 110.6% +/- 79.0% and 114.1% +/- 81.7% in Cmax0-5 and AUC0-5, respectively, with a prolongation of mean Tmax 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 AUC0-24, 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 the systemic availability of ganciclovir, it is recommended that patients be instructed to take each dose of ganciclovir with food.
Jung
D
D
Roche Global Development, Palo Alto, California, USA.
Griffy
K
K
Dorr
A
A
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D005215:Fasting / Q000097:blood; D018565:Food-Drug Interactions; D015774:Ganciclovir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006679:HIV Seropositivity / Q000097:blood / Q000378:metabolism*; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged
D000998:Antiviral Agents; D015774:Ganciclovir