Effect of omeprazole on the bioavailability of unmodified and phospholipid-complexed aspirin in rats.
BACKGROUND
Treatment and prevention of non-steroidal anti-inflammatory drug-induced gastropathy involve the concurrent use of antisecretory drugs. Recently, we have shown that the ability of these drugs to increase the intragastric pH to values > > pKa of NSAIDs compromises their therapeutic activity. In the present study, we evaluated the potential of omeprazole to interfere with the bioavailability of aspirin administered to rats either alone or complexed with the zwitterionic phospholipid, dipalmitoylphosphatidylcholine (DPPC).


METHODS
Aspirin or aspirin/DPPC was administered intragastrically to rats pre-dosed with either saline or omeprazole. Concentrations of aspirin and salicylic acid in the blood and the gastric mucosa were assessed by HPLC and the 6-keto-PGF1 alpha gastric mucosal concentration by radioimmunoassay.


RESULTS
Gastric absorption of aspirin and its relative bioavailability were reduced by an antisecretory dose of omeprazole; its inhibitory effect on gastric prostaglandin synthesis was consequently attenuated. However, these effects could be partly overcome if aspirin was administered as a complex with DPPC.


CONCLUSIONS
These observations suggest that: (i) DPPC increases the lipid solubility and gastric permeability of NSAIDs; and (ii) neutralization of the gastric pH results in a shift of aspirin absorption toward the intestine where it could be degraded to salicylic acid.
Giraud
M N
MN
Department of Integrative Biology, Pharmacology and Physiology, University of Texas-Houston Medical School, Houston 77030, USA.
Sanduja
S K
SK
Felder
T B
TB
Illich
P A
PA
Dial
E J
EJ
Lichtenberger
L M
LM
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001241:Aspirin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D004337:Drug Carriers; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D009500:Neutralization Tests; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D015060:1,2-Dipalmitoylphosphatidylcholine; D015121:6-Ketoprostaglandin F1 alpha; D009853:Omeprazole; D001241:Aspirin