Intestinal absorption of drugs. I: The influence of taurocholate on the absorption of dantrolene in the small intestine of the rat.
The influence of sodium taurocholate (1) on the intestinal absorption of the lipophilic drug dantrolene (2) was studied in vivo in a chronically isolated internal loop in the rat. Concentrations of 2 were kept below the saturation concentration in saline. Absorption kinetics of 2 were evaluated on the basis of steady-state blood levels, which develop during single-pass perfusions, and on the basis of the rate of disappearance of the drug from the perfusate during recirculating perfusions. Compound 1 at a concentration of 10 mM in the perfusate induced a twofold reduction of the absorption rate compared with the same concentration of 2 in saline. Pretreatment of the absorptive surface with a 10 mM solution of 1 had no detectable effect on the absorption rate of 2 in saline. After perfusions with 10 mM solutions of 1, the perfusate concentration of proteins, phosphorus, and hexoses in the effluent was increased. The reduction of the absorption rate can be ascribed mainly to a reduction of the thermodynamically active concentration of 2 as calculated from the phase-separation model. In addition, 10 mM 1 seems to temporarily increase the barrier function of the mucous layer.
Poelma
F G
FG
Department of Pharmaceutics, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Tukker
J J
JJ
Crommelin
D J
DJ
D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003620:Dantrolene / Q000493:pharmacokinetics*; D004058:Diffusion; D006601:Hexoses / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010758:Phosphorus / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology*
D006601:Hexoses; D011506:Proteins; D010758:Phosphorus; D013656:Taurocholic Acid; D003620:Dantrolene