Effect of Bile Salts on Gastric Emptying and Intestinal Transit in the Rat (original) (raw)
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Transport of drugs in isolated hepatocytes the influence of bile salts
Biochemical Pharmacology, 1978
The influence of bile salts on hepatic transport of drugs was studied using isolated hepatocyte suspensions. Upra~e of the organic anions, dibromosulphthalein (DBSP), indcrcyanine green (ICG) and an organic cation, N4-acetyi procainamide ethobromide (APAEB) was measured. Afte; 60 min incubation the amount of DBSP, ICG and APAEB nresent in the cells was 17. 41 and 4.5 ner cent of the added amount respectively. The release of DBSP, ICG and APAEB from the hepatocytes preincubated with the agents under study, after 60 min incubation in fresh medium was 80.5, 12.5 and 48.9 per cent of the amount initially present respectively. The presence of bile canalicular membranes in the isolated hepatocytes was demonstrated by enzymehistochemistry: 5'nucleotidase activity showed sharp branched bands over the cell surface. When bile salts were present in the incubation medium. the cellular content of DBSP, ICG and APAEB was diminished. The taurocholate concentration which caused 50 per cent of the maximal effect was 0.07mM. O.lOmM and 0.06mM in experiments with DBSP, ICG and APAEB respectively. Pharmacokinetic analysis revealed that the influence of bile salts on cellular content of the three compounds was due to inhibition of the uptake into the isolated hepatocytes, rather than stimulation of release from the cells. The hypothesis, that stimulation of biliary output of organic anions in viw is due to a modifying effect of bile salts on the canalicular membranes. instead of being the result of the increased bile flow, is not supported by this study.
Pharmacology of bile acids and their derivatives: Absorption promoters and therapeutic agents
European Journal of Drug Metabolism and Pharmacokinetics, 2006
The role of bile acids in pharmacotherapy is reviewed in this article. The therapeutic use of bile has been recognized since ancient times. Previously bile acids were the standard treatment for gallstones where chenodeoxycholic acid and ursodeoxycholic acid were effective in promoting the dissolution of cholesterol gallstones. Today their therapeutic role looks set to expand enormously. Bile acids as absorption promoters have the potential to aid intestinal, buccal, transdermal, ocular, nasal, rectal and pulmonary absorption of various drugs at concentrations that are non-toxic. Keto derivatives of cholic acid, such as 3a,7a,dihydroxy-12-keto-5a-cholic acid (sodium salt and methyl ester) are potential modifiers of blood-brain barrier transport and have been shown to promote quinine uptake, enhance the analgesic effect of morphine and prolong the sleeping time induced by pentobarbital. They have also been shown to be hypoglycaemic. Bile acids as therapeutic agents have the potential to produce beneficial effects in sexually transmitted diseases, primary biliary cirrhosis, primary sclerosing cholangitis, gallstones, digestive tract diseases, cystic fibrosis, cancer and diabetes.
Colonic absorption of unconjugated bile acids
Digestive Diseases and Sciences, 1979
Colonic absorption of three major unconjugated bile acids-cholate, chenodeoxycholate, and deoxycholate-was measured under steady-state conditions using a technique of co-Ionic perfusion in healthy volunleers. Aqueous solutions at pH 8.0 and varying in concentration from 1 mM to 10 mM were used. The rate of chenodeoxycholate absorption averaged nine times that of cholate absorption; deoxycholate absorption was somewhat less than that of chenodeoxycholate absorption, averaging six times that of cholate. At concentrations below 5 mM, the rate of absorption of bile acids was directly proportional to concentration, so that "clearance" could be calculated. Clearance values for a 1-mM solution (ml/min/colon, mean +_ SE) were: chenodeoxycholate, 9.84 +_ 1.0; deoxycholate, 7.0 +-1; and cholate, 0.82 +_ 0.10. Since absorption was proportional to concentration in the lumen, and was more rapid for the dihydroxy acids, the major mechanism of absorption was thought to be passive nonionic diffusion. Maximal rates of bile acid absorption were calculated from a l-mM solution and found to be as high as 4.2 g/day for chenodeoxycholate, 3.2 g/day for deoxycholate, and 0.5 g/day for cholate, and the rate would be still greater for more concentrated solutions. Colonic absorption may contribute significantly to conservation of the dihydroxy bile acid pool, especially in conditions of bile acid malabsorption. Bile acids secreted into the proximal intestine are conserved efficiently by active absorption in the ileum (2-5) augmented by passive absorption throughout the intestine (5-10). Previous experiments in man have quantitated passive bile acid absorption in the jejunum (8-10) and ileum (i0, 11) and have also provided evidence that bile acids can be absorbed from the colon (12, 13). To date, there
Absorption-Enhancing Effects of Bile Salts
Molecules, 2015
Bile salts are ionic amphiphilic compounds with a steroid skeleton. Among the most important physiological properties of bile salts are lipid transport by solubilization and transport of some drugs through hydrophobic barriers. Bile salts have been extensively studied to enhance transepithelial permeability for different marker molecules and drugs. They readily agglomerate at concentrations above their critical micelle concentration (CMC). The mechanism of absorption enhancement by bile salts appears to be complex. The aim of the present article was to review bile salt structure and their application as absorption enhancers and the probable mechanism for increasing permeation based on previous studies.
Quarterly journal of experimental physiology (Cambridge, England), 1984
The influence of two different anaesthetics, sodium pentobarbitone and ethyl urethane, on the enhancement of maximal bilirubin and bromosulphthalein (BSP) excretion induced by bile salts was investigated in rabbits. Two micelle-forming (glycodeoxycholate and taurocholate) and one non-micelle-forming (dehydrocholate) bile salts were used. Under urethane anaesthesia the bile flow was lower than with pentobarbitone, and this could be attributed to a smaller bile salt non-dependent fraction of secretion. The effect of bile salts on the maximal excretion of the two organic anions appeared more clearly related to some kind of micelle interaction in rabbits anaesthetized with urethane than in pentobarbitone-anaesthetized animals. Thus, under urethane, infusions of glycodeoxycholate substantially increased the maximal excretion of bilirubin and BSP, taurocholate exerted an intermediate and dehydrocholate only a small effect. Under pentobarbitone, however, the augmenting action of all three ...
Bile Increases Intestinal Lymphatic Drug Transport in the Fasted Rat
Pharmaceutical Research, 2005
Purpose. This study was conducted to determine the influence of (1) the source of recruited endogenous fatty acid (FA), and (2) bile on intestinal lymphatic transport of halofantrine (Hf) in fasted rats. Methods. Endogenous FA output in bile, and exogenous ( 14 C radiolabeled) FA, endogenous FA, and Hf transport in mesenteric lymph were determined following administration of low dose lipid formulations containing either 4 or 40 mg of exogenous FA [oleic acid (OA)] and different amounts of bile salt (BS) and lysophosphatidylcholine (LPC) to fasted rats. Results. Administration of 40 mg of OA recruited endogenous FA and Hf transport into intestinal lymph, whereas 4 mg OA did not. However, addition of BS to the 4-mg OA dose led to stimulation of endogenous FA recruitment into lymph and an increase in lymphatic transport of Hf and endogenous FA output in bile. Addition of LPC to the 4-mg OA dose (dispersed in BS) caused a substantial increase in endogenous FA transport in lymph; however, no coincident increase in either lymphatic transport of Hf or endogenous FA output in bile was observed. Conclusion. Biliary-derived endogenous FA has a higher propensity to support lymphatic transport of Hf compared to other sources of endogenous FA. The results suggest that this is related to the disparate trafficking of these alternate sources of endogenous FA within the enterocyte.