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Eur J Pharm Biopharm. 2017 Mar;112:75-84. doi: 10.1016/j.ejpb.2016.10.027. Epub 2016 Nov 16.

Exploring the link between gastric motility and intragastric drug distribution in man.

Author information

1
Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - Box 921, 3000 Leuven, Belgium. Electronic address: jens.vandenabeele@kuleuven.be.
2
Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - Box 921, 3000 Leuven, Belgium. Electronic address: joachim.brouwers@kuleuven.be.
3
Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: jan.tack@med.kuleuven.be.
4
Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - Box 921, 3000 Leuven, Belgium. Electronic address: patrick.augustijns@kuleuven.be.

Abstract

In drug development, the stomach is often considered to be a simple, one-compartmental organ, a waiting room for transfer of an orally administered dosage form to the duodenum. However, factors such as gastric acidity and hydrodynamics in the gastric environment may influence drug disposition. Although a link between gastrointestinal drug behaviour and gastric motility has often been hypothesized, they have not been simultaneously investigated in humans yet. In this proof-of-concept study, the combination of a well-established intraluminal sampling technique with high-resolution manometric measurements in the gastrointestinal tract was evaluated. This new combination of in vivo techniques proved to be feasible from a practical point of view and yielded valuable additional information regarding intraluminal drug behaviour. As a first application, the link between fasted state gastric motility and (in)homogeneous distribution of an orally administered drug in the stomach was investigated in healthy subjects. To this end, drug concentrations were measured in different regions of the stomach after oral administration of a commercially available drug product (Gabbroral®, 250mg paromomycin) during a specific period of gastric contractile activity. A clear trend towards better mixing of an orally administered drug with gastric contents was observed when dosed in the presence of gastric contractions, resulting in a more homogeneous distribution of the drug throughout the stomach compared to dosing in the absence of gastric contractions.

KEYWORDS:

Biopharmaceutics; Clinical trial; Drug distribution; Gastrointestinal; Motility; Oral drug delivery; Stomach

PMID:
27865990
DOI:
10.1016/j.ejpb.2016.10.027
[Indexed for MEDLINE]

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