Inhibition of colchicine absorption by the fat substitutes, sucrose polyester and tricarballylate triester, in the rat.
The effect of non-absorbable fat substitutes (sucrose polyester (SPE) and tricarballylate triester (TCTE)) on the enterohepatic circulation of colchicine was studied in the rat. In a first experiment, emulsions of either sunflower oil (SFO), SPE, or TCTE, were introduced into the ligated small intestine and compared to a control group receiving physiological saline. All the groups received colchicine as an intravenous bolus. The plasma levels of colchicine in all groups was not affected, and luminal samples indicated that SPE and TCTE have no influence on the biliary excretion of colchicine (a previous experiment in bile duct-cannulated rats showed that SPE and TCTE, introduced by intragastric tube, have no effect on bile flow rate). In a second experiment, colchicine diluted in bile was mixed with saline or emulsions of either SFO, SPE or TCTE, and introduced into the ligated small intestine. The area under the curve and the maximal plasma concentration of colchicine were reduced when the drug was mixed with SPE or TCTE rather than saline (p < 0.0005). After 150 min, luminal samples were taken and showed significantly higher (p < 0.034) concentrations of colchicine in both SPE and TCTE groups compared to the saline group, indicating a significant inhibition of reabsorption of biliary colchicine. In conclusion, the non-absorbable fat substitutes, SPE and TCTE, did not influence biliary excretion of colchicine but reduced its reabsorption, thus altering its enterohepatic circulation.
Benmoussa
K
K
INSERM U26, Hôpital Fernand WIDAL, Paris, France.
Scherrmann
J M
JM
Bourre
J M
JM
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001646:Bile / Q000502:physiology; D002250:Carbon Radioisotopes; D003078:Colchicine / Q000493:pharmacokinetics*; D004044:Dietary Proteins / Q000494:pharmacology*; D004347:Drug Interactions; D004655:Emulsions; D004764:Enterohepatic Circulation / Q000187:drug effects / Q000502:physiology; D019358:Fat Substitutes; D005227:Fatty Acids / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000031:analogs & derivatives* / Q000494:pharmacology; D014233:Tricarboxylic Acids / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D002250:Carbon Radioisotopes; D004044:Dietary Proteins; D004655:Emulsions; D019358:Fat Substitutes; D005227:Fatty Acids; D014233:Tricarboxylic Acids; D011092:Polyethylene Glycols; D013395:Sucrose; C013692:sucrose polyester; C028021:tricarballylic acid; D003078:Colchicine