Stability of oleuropein in the human proximal gut.
OBJECTIVE
We aimed to assess the intralumenal stability of oleuropein in human gastric and small intestinal contents. We additionally aimed to assess the stability characteristics of oleuropein in media simulating the intralumenal conditions.


METHODS
The intralumenal stability of oleuropein was assessed in aspirates from the stomach and the upper small intestine of healthy volunteers collected under both fasted and fed state conditions and in media simulating the intralumenal environment.


RESULTS
Oleuropein degraded in aspirates collected in the fasted state. When the initial concentration was about 50 microg/ml (close to expected intragastric concentration after single dose of commercially available products of oleuropein) the mean zero-order half-life of oleuropein in aspirates collected from the fasted small intestine was estimated to be 3.14 +/- 0.08 h at 37 degrees C (i.e. after oral administration in the fasted state, a substantial fraction of oleuropein degrades before reaching the intestinal mucosa). In contrast, oleuropein was stable in aspirates collected from the fed stomach; in small intestinal contents aspirated in the fed state the estimated zero-order degradation half-life was at least 12 h.


CONCLUSIONS
These data suggest that oleuropein should not have substantial intralumenal stability problems when administered in the fed state. Data collected in media simulating the intragastric and intraintestinal environment suggest that pH affects the stability of oleuropein only at low pH values (of about 2). At higher pHs degradation characteristics are at least partly affected by the presence of other scavengers of reactive oxygen species in the medium.
Markopoulos
Constantinos
C
Department of Pharmaceutical Technology, Faculty of Pharmacy, National & Kapodistrian University of Athens, Zografou, Greece.
Vertzoni
Maria
M
Agalias
Apostolos
A
Magiatis
Prokopios
P
Reppas
Christos
C
D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005215:Fasting; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D005766:Gastrointestinal Contents / Q000737:chemistry* / Q000187:drug effects*; D006801:Humans; D006851:Hydrochloric Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D057888:Iridoid Glucosides; D039823:Iridoids; D031658:Olea / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D019518:Postprandial Period; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013270:Stomach / Q000187:drug effects
D016166:Free Radical Scavengers; D057888:Iridoid Glucosides; D039823:Iridoids; D011714:Pyrans; C002769:oleuropein; D006851:Hydrochloric Acid