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• W2008400345 abstract "Abstract In the United States and other countries, non-steroidal anti-inflammatory drugs (NSAIDs) can be purchased without a prescription. Due to their widespread use, the drugs' most common side effect, gastric toxicity, becomes a more serious concern. Gastric toxicity can occur directly by contact with mucous membranes or indirectly by the inhibition of prostaglandin production in the gastric mucosa. We have studied the uptake of NSAIDs in gastric tissue, specifically parietal cells removed from the rabbit stomach. New Zealand White rabbits were killed and then used to harvest parietal cells. The purified cells were used to study the uptake of ibuprofen, indomethacin and ketoprofen (NSAIDs) over time and under different experimental conditions. The effects of concentration were investigated for all three NSAIDs. In addition, indomethacin and ibuprofen were used to investigate the mechanism of uptake. Studies were determined for the effects of varied extracellular pH from pH 6 to 8, and inhibitory conditions from depressed temperature (5°C), metabolic inhibitors (sodium azide and 2,4-dinitro-phenol), an ionophore (nigericin) and a sodium free support medium. The interaction of NSAIDs with lysed parietal cells was investigated also. Initial rate data indicated that Michaelis-Menten kinetics were apparent; however, poor solubility of all three NSAIDs prevented complete characterization of the inclusion of a passive transport mechanism. Uptake showed a statistically significant increase (P = 0.01 to 0.05) as pH decreased, also suggesting contribution from a passive mechanism. Studies with inhibitors showed minimal effects. However, uptake at equilibrium for the ionophore, nigericin, showed a 10-fold increase over the control for ibuprofen (P = 0.005) and a 1.4-fold increase for indomethacin (P = 0.04). Depressed temperature (5°C) increased the initial rate and uptake at equilibrium 2.1- and 2.2-fold, respectively, for ibuprofen (P &lt; 0.01). For indomethacin depressed temperature increased the initial rate and uptake at equilibrium 2.7- and 5.2-fold, respectively (P &lt; 0.01). The increases at 5°C suggests that adsorption may be an important uptake component. Experiments with lysed parietal cells showed a non-specific uptake phenomenon, suggesting an adsorption component was occurring also." @default.
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• W2008400345 date "2000-05-01" @default.
• W2008400345 modified "2023-09-26" @default.
• W2008400345 title "Uptake of Ibuprofen, Indomethacin and Ketoprofen into Isolated Rabbit Parietal Cells" @default.
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• W2008400345 doi "https://doi.org/10.1211/0022357001774282" @default.
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