-Purpose. Oral drug administration remains the most common and most convenient way used in clinical therapy. The availability of a simple, rapid, economic and reproducible in vitro method to assess the rate, extent and mechanism of intestinal drug absorption is a very helpful tool. The purpose of this study was to compare the performance of Sartorius SM 16750 Absorption Simulator apparatus to Everted Gut Sac (EGS) technique in terms of predicting drug permeability. Methods. Permeation studies across these two in vitro models were performed with six drugs selected across the Biopharmaceutics Classification System (BCS) categories: tramadol (class I of BCS), doxycycline (class I of BCS), diclofenac (class II of BCS), clopidogrel (class II of BCS), metformin (class III of BCS) and chlorothiazide (class IV of BCS). Results. Apparent permeability coefficient (P app ) and diffusion profiles obtained with EGS and Sartorius SM 16750 apparatus were similar for diclofenac and metformin, whereas, we noticed significant differences (p≤0.05), for tramadol, doxycycline, clopidogrel and chlorothiazide. Conclusion. Compared to Everted Gut Sac model, Sartorius SM 16750 absorption simulator apparatus seems to have limited application for the assessment of intestinal drug absorption since it does not take into consideration the involvement of others processes than the passive transcellular pathway as mechanism of drug absorption. _______________________________________________________________________________________
Naringin, a natural compound which has no undesirable side effects as compared with quinidine, could be used as a pharmaceutical excipient in the presence of clopidogrel solid dispersions to increase clopidogrel intestinal absorption and therefore its oral bioavailability.
The everted gut sac technique has been used to investigate the effect of Vibrio vulnificus on water and electrolyte (Na(+), K(+), Cl(-), HCO(3)(-)) transport on the intestine of sea bream (Sparus aurata L.). Both the anterior and the posterior intestine were incubated in a medium containing 10(8) V. vulnificus cells ml(-1) at 25 degrees C for 2 h. The presence of V. vulnificus resulted in a significant reduction (P < 0.05) of water absorption in the anterior intestine, while sodium absorption in the anterior (P < 0.01) and posterior (P < 0.05) intestine was elevated. Chloride absorption was increased, but the changed was not significant, while potassium absorption decreased significantly (P < 0.05), but only in the posterior intestine. Incubation the sea bream intestine with V. vulnificus did not affect carbonate secretion in the anterior segment, whereas high secretion was stimulated in the posterior segment (P < 0.01). Histological evaluations demonstrated damage in the anterior intestine of sea bream that was characterized by the detachment of degenerative enterocytes, alterations in the microvilli, and the presence of a heterogenous cell population, indicating inflammation. Based on our results, we conclude that V. vulnificus caused cell damage to the intestine of sea bream and that the anterior intestine is more susceptible than the posterior part of the intestine. Several hypotheses are suggested to explain our observations, such as the presence of higher numbers of villosities in the anterior intestine than in the posterior one and/or the presence of endogenous bacteria in the posterior intestine which may have a protector role.
Etidronate has specific site and bone cell actions in the periodontium. It inhibits the osteoclast differentiation induced by ovariectomy in the apposition side of the periodontium but maintains bone formation over all the socket surfaces. Such specificity may be related to the pathogenesis of the bisphosphonate-induced osteonecrosis of the jaw.
In the goose, alanine and arginine, intravenously or orally administered, act in the same way on pancreatic hormones; they both stimulate insulin and glucagon secretions. Conversely, whereas alanine treatment has no effect on plasma gut GLI, oral arginine stimulates gut GLI secretion. Since stimulation of gut GLI secretion does not occur with i.v. arginine, it may be assumed that this secretion depends on the intestinal transit of arginine and, as already described (Sitbon and Mialhe 1979), of glucose. The results, compared with studies on a similar species (duck) and on mammals, point out that i.v. infusion of alanine stimulates IRI and GLI secretions in the goose and not in the duck. In the same way, arginine i.v. infusion, contrarily to the observation made in the duck, is without effect on gut GLI secretion in the goose. Furthermore, insulin seems to be able to inhibit the alpha cell response to arginine infusion, as in mammals, whereas this is not the case in ducks.
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