Formulation-dependent food effects demonstrated for nifedipine modified-release preparations marketed in the European Union.
The objective of this study was a comparative investigation of the influence of concomitant food intake on the bioavailability of two nifedipine-containing controlled-release formulations. Adalat OROS and CORAL were compared in a randomised, non-blind, four-way crossover design in 24 healthy, male subjects after single dose administration following a high fat American breakfast or an overnight fast of 12 h, respectively. Plasma samples were withdrawn until 48 h post-dose. In the fasted state, the bioavailability (AUC and C(max) values) was lower for CORAL than for Adalat OROS. Under fed conditions, differences in bioavailability between both products were markedly increased. With respect to the therapeutic use of both products, the most important finding was the significant dose-dumping effect observed after fed administration of CORAL, resulting in nifedipine plasma concentrations of nearly three- to four-fold in 11 of 24 volunteers. The mean ratio of C(max) was 235% comparing CORAL with Adalat OROS under these conditions. The formulation-dependent food interaction observed in this study may be therapeutically relevant, especially in the case of changing administration conditions or switching from one product to the other.
Schug
Barbara S
BS
SocraTec R&D, Feldbergstr. 59, D-61440 Oberursel, Germany. barbara.schug@socratec-pharma.de
Brendel
Erich
E
Wolf
Dörte
D
Wonnemann
Meinolf
M
Wargenau
Manfred
M
Blume
Henning H
HH
D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood; D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004041:Dietary Fats / Q000378:metabolism*; D004304:Dosage Forms; D004345:Drug Industry; D005062:European Union; D005215:Fasting / Q000097:blood*; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000097:blood*
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D004304:Dosage Forms; D009543:Nifedipine