Cyclosporin absorption is impaired 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 cyclosporin A (CsA) intestinal absorption was studied in the rat using in situ perfusion and gastric intubation techniques. A first experiment using the recirculating intestinal perfusion model showed that emulsions of either 5% SPE or TCTE significantly reduced (p < 0.0008) CsA absorption, whereas no difference was found between results for saline and 5% olive oil emulsion. In single-pass intestinal perfusion experiments SPE dose-dependently inhibited CsA absorption at SPE concentrations of 0.31% (p < 0.0004) and higher. Using gastric intubation, whole blood CsA concentrations significantly decreased when administered with SPE and TCTE in comparison with olive oil (p < 0.04). These results confirm that the CsA fraction dissolved in the undigested oil phase, constituted by the undigested and nonabsorbed fat substitute, is unavailable for intestinal absorption.
INSERM U26, H pital Fernand Widal, Paris, France.
K
K
Benmoussa
A
A
Sabouraud
J M
JM
Scherrmann
J M
JM
Bourre
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004952:Esters / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007441:Intubation, Gastrointestinal; D008297:Male; D000069463:Olive Oil; D010477:Perfusion; D010938:Plant Oils / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013395:Sucrose / Q000031:analogs & derivatives* / Q000494:pharmacology; D014233:Tricarboxylic Acids / Q000494:pharmacology*
D004042:Dietary Fats, Unsaturated; D004952:Esters; D005227:Fatty Acids; D000069463:Olive Oil; D010938:Plant Oils; D014233:Tricarboxylic Acids; D013395:Sucrose; C013692:sucrose polyester; D016572:Cyclosporine; C028021:tricarballylic acid