Intestinal absorption of tolfenamic acid at experimental malabsorption states in rats.
Absorption kinetics of 14C-labelled N-(3-chloro-o-tolyl)-anthranilic acid (tolfenamic acid, 14C-TA, Clotam) from the small intestine was studied in intact rats and in rats with malabsorption states provoked by methotrexate, starvation, and triparanol. 14C-TA was administered intravenously and intraduodenally, and the drug concentrations in the blood were followed up radiometrically. A multi-compartmental model was applied for mathematical analysis. Theoretical model parameters were computed, and absorption parameters were then derived from the theoretical ones. The absorption half-life of 14C-TA was 5.3 min in the controls, 10.8 min in the methotrexate-intoxicated, 7.5 min in the fasted, and 5.3 min in the triparanol-intoxicated rats. The absorbed fraction of the intraduodenal 14C-TA dose was 100% in each experimental group as well as in the controls. It is suggested that the slower transfer of 14C-TA through the intestinal barrier in the methotrexate-intoxicated and fasted rats may be caused by the reduction of the absorptive surface.
D000818:Animals; D005260:Female; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000503:physiopathology; D008286:Malabsorption Syndromes / Q000139:chemically induced / Q000378:metabolism*; D008727:Methotrexate; D051381:Rats; D011919:Rats, Inbred Strains; D062367:ortho-Aminobenzoates / Q000378:metabolism*
D062367:ortho-Aminobenzoates; C009500:tolfenamic acid; D008727:Methotrexate