Impact of the intragastric location of extended release tablets on food interactions.
Gastrointestinal motility and transport as well as concomitant food intake are factors that are known to influence pharmacokinetics derived after intake of extended release dosage forms. However, the mechanisms behind these influencing factors are mostly unknown. In this study the gastrointestinal transit and the in vivo drug release of magnetically labelled extended release tablets containing felodipine were monitored together with the drug absorption phase of pharmacokinetics under fasting and fed conditions in six healthy volunteers using Magnetic Marker Monitoring. It was found that the in vivo drug release profiles of the tablets compared well under fasting and fed conditions. However, the plasma concentration profiles were strongly influenced by concomitant food intake. This could be attributed to elongated residence of the tablets in proximal parts of the stomach, resulting in delayed drug absorption and the occurrence of late high plasma peak concentrations. The lag time until the first appearance of felodipine in plasma and the residence time of the tablets in the proximal stomach, were found to be directly correlated. The study shows that increased plasma peak drug concentrations after intake of extended release formulations together with food can be explained by poor mixing in the proximal part of the stomach and are not necessarily due to failure of the formulation to control drug release (dose dumping).
Weitschies
Werner
W
Institute of Pharmacy, University of Greifswald, Friedrich-Ludwig-Jahn-Strasse 17, 17487 Greifswald, Germany. werner.weitschies@uni-greifswald.de
Wedemeyer
Ralph-Steven
RS
Kosch
Olaf
O
Fach
Kilian
K
Nagel
Stefan
S
Söderlind
Erik
E
Trahms
Lutz
L
Abrahamsson
Bertil
B
Mönnikes
Hubert
H
D000328:Adult; D000465:Algorithms; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D015736:Felodipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D018565:Food-Drug Interactions; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000378:metabolism*; D005772:Gastrointestinal Transit / Q000502:physiology; D006801:Humans; D008280:Magnetics; D008297:Male; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D015736:Felodipine