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.
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.
Authors: Saskia H Meves; Thomas Hummel; Heinz G Endres; Nora Mayböck; Andreas F C Kaiser; Kay D Schröder; Katja Rüdiger; Ursula Overbeck; Achim Mumme; Andreas Mügge; Horst Neubauer Journal: J Thromb Thrombolysis Date: 2014 Impact factor: 2.300
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Authors: Ana María Pello Lázaro; Carmen Cristóbal; Juan Antonio Franco-Peláez; Nieves Tarín; Álvaro Aceña; Rocío Carda; Ana Huelmos; María Luisa Martín-Mariscal; Jesús Fuentes-Antras; Juan Martínez-Millá; Joaquín Alonso; Óscar Lorenzo; Jesús Egido; Lorenzo López-Bescós; José Tuñón Journal: PLoS One Date: 2017-01-19 Impact factor: 3.240
Authors: Masafumi Ono; Yoshinobu Onuma; Hideyuki Kawashima; Hironori Hara; Chao Gao; Rutao Wang; Neil O'Leary; Edouard Benit; Luc Janssens; Maurizio Ferrario; Aleksander Żurakowski; Marcello Dominici; Kurt Huber; Paweł Buszman; Scot Garg; Joanna J Wykrzykowska; Jan J Piek; Peter Jüni; Christian Hamm; Stephan Windecker; Pascal Vranckx; Efthymios N Deliargyris; Deepak L Bhatt; Robert F Storey; Marco Valgimigli; Patrick W Serruys Journal: Catheter Cardiovasc Interv Date: 2022-05-02 Impact factor: 2.585