We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics.
- Authors
Huppertz, Andrea; Bollmann, Johanna; Behnisch, Rouven; Bruckner, Thomas; Zorn, Markus; Burhenne, Jürgen; Haefeli, Walter E.; Czock, David
- Abstract
Food reduces tacrolimus bioavailability after immediate‐release tacrolimus (IR‐Tac) and after a new prolonged‐release tacrolimus formulation (PR‐Tac), when using a high‐fat breakfast, but the effects of a continental breakfast on PR‐Tac are unknown. In an open‐label, 4‐phase, randomized, 2‐sequence, crossover pharmacokinetic trial, 36 healthy volunteers (18 females) received single 5‐mg tacrolimus doses as PR‐Tac and as IR‐Tac fasted or with a standardized continental breakfast. Tacrolimus pharmacokinetics were analyzed using noncompartmental methods and mixed‐model analysis of variance. The continental breakfast significantly decreased average tacrolimus exposure (area under the plasma concentration–time curve) with both preparations (IR‐Tac, 67%; 90% confidence interval [CI], 59%‐75%; P <.01; and PR‐Tac, 79%; 90%CI, 70%‐89%; P <.01) with a nonsignificant difference between both preparations (P =.10). The maximum concentration (Cmax) and the time to maximum concentration (tmax) were significantly affected only after IR‐Tac (Cmax IR‐Tac, 39%; 90%CI, 34%‐45%; P <.01; and PR‐Tac, 87%; 90%CI, 76%‐101%; P =.11; tmax IR‐Tac, 212%, 90%CI, 179%‐252%; P <.01; and PR‐Tac, 101%; 90%CI, 86%‐120%; P =.89), which was significantly different between both preparations (P <.01). Considering switching from IR‐Tac to PR‐Tac, predicted dose requirements differed according to the timing of drug intake in relation to food. In conclusion, a continental breakfast decreased average tacrolimus exposure of both preparations to a similar extent. Cmax and tmax were affected only after IR‐Tac. The effect of a standardized continental breakfast on PR‐Tac was considerably smaller than previously reported effects of a high‐fat breakfast on PR‐Tac.
- Subjects
BREAKFASTS; BIOAVAILABILITY; CROSSOVER trials; ANALYSIS of variance; CONFIDENCE intervals
- Publication
Clinical Pharmacology in Drug Development, 2021, Vol 10, Issue 8, p899
- ISSN
2160-763X
- Publication type
Article
- DOI
10.1002/cpdd.924