ABSTRACT
PURPOSE: Monitoring the distribution of drugs or drug delivery systems in the human gastrointestinal tract is an important prerequisite for the design of orally administered drugs. We investigated the intragastric distribution of a colloidal drug delivery system (liposomes containing the contrast agent Gd-DOTA) by magnetic resonance imaging. METHODS: Following ingestion of a liquid or a solid meal, gastric distribution of liposomes released from a capsule and the fat component of the solid meal were tracked in 7 healthy subjects for 90 min. Liposomes were identified in gastric content by the increased signal intensity provided by the encapsulated Gd-DOTA. RESULTS: With the liquid meal, liposomes initially formed a layer on the surface before distributing in 86 +/- 2% of gastric content (maximum distribution volume) within 42 +/- 6 min. With the solid meal, maximum distribution (7 +/- 1%, reached within 24 +/- 6 min) was confined to a small volume in the fundus without forming a layer, suggesting that distribution was related to the accessible liquid compartment. Fat distribution was inhomogeneous and concentrated in the fundus. CONCLUSIONS: Intragastric distribution of a colloidal drug carrier model, such as Gd-DOTA-filled liposomes, varies between meals of different composition. These differences can be monitored in three dimensions in humans by MRI.
Subject(s)
Digestive System/metabolism , Drug Carriers/pharmacokinetics , Drug Monitoring/methods , Liposomes/pharmacokinetics , Magnetic Resonance Imaging/methods , Adult , Colloids , Dietary Fats/pharmacokinetics , Female , Food-Drug Interactions/physiology , Humans , Male , Statistics, NonparametricSubject(s)
Oligonucleotides, Antisense/metabolism , Base Sequence , Biological Transport , Cholesterol Esters/metabolism , Codon , Genes, ras , Humans , Molecular Sequence Data , Oligonucleotides, Antisense/chemical synthesis , Porphyrins/metabolism , Tumor Cells, Cultured , Urinary Bladder NeoplasmsABSTRACT
From the stembark of Tabernaemontana crassa the alkaloid ibogaine was isolated as the major component. Ibogaine showed activity against the gram-positive Bacillus subtilis. Conopharyngine was identified as one of the minor compounds.
