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Characteristics Of Ketoprofen Transport Through Rat Jejunum 'in Vitro'

出版	2002
URL	http://books.google.com.hk/books?id=zCV8rgEACAAJ&hl=&source=gbs_api

註釋To evaluate the influence of microclimate pH on the mucosal surface and to determine the role of monocarboxylic acid transporter 1 (MCT1) in ketoprofen transport through isolated intestinal tissue. Methods. The permeability of nonsteroidal antiinflammatory drug ketoprofen (monocarboxylic acid, pKa = 4.6)through rat jejunum was examined in side by side diffusion cells under short - circuit conditions with fluorescein sodium as an integrity marker. Microclimate pH was measured by flat membrane pH microelectrode. Results. Polarised transport of ketoprofen across rat jejunum in mucosal to serosal (m-to-s) and serosal to mucosal (s-to-m) direction was observed (Pappm-to-s = 19.1x10-6 cmžs, Papps-to-m = 11.4x10-6 cmžs) when both sides of the tissue were bathed with standard Ringer buffer pH = 7.51. When mucus disrupting agent1,4-dithio-DL-threitol (2mM) was added to the mucosal side, microclimate pH increased from 7.08 to 7.21 and no polarised transport in m-to-s and s-to-mdirection was observed. Additionally Papp values of ketoprofen increasedfor 3 fold when pH of incubation medium was changed from 8.06 (microclimate pH was 7.34) to 6.07 (microclimate pH was 5.95). The addition ofmetabolic inhibitor sodium azide to the bathing solution significantly increased microclimate pH and reduced ketoprofen transport in m-to-s direction. There is probably no contribution of MCT1 in ketoprofen transport across rat jejunum because no influence of acetate (10 and 20mM), benzoate (2mM), L-lactate (20mM) (all three substances are substrates for MCT1) and also of MCT1 inhibitor &šalphađ-cyano-4-hydroxy-cinnamic acid (1mM) on the rate of ketoprofen transport was established. Moreover, the effect of different ketoprofen concentrations in donor solution on ketoprofen Papp values was negligible. Conclusion. The results of the present study suggest that ketoprofen is probably transported across the rat jejunum according to the modified pH - partition theory while the contribution of any other transporters (different from MCT1) can not be excluded.