In vivo absorption of phenytoin from rat small intestine and its inhibition by phlorizin.
In vivo absorption of phenytoin from the small intestine was studied by an in vivo closed segment technique. Phenytoin in concentrations of 1000, 2000, and 4000 mumol/l was administered in dissolved form. Polythylene glycol 4000 was used as a non-absorbable marker. The concentrations of phenytoin in the intestinal lumen, in the mucosa, and in cardiac blood were measured both by spectrophotometry and by gas chromatography. Phenytoin was absorbed very rapidly, and the proportion absorbed increased with increasing dose. Thus, during the first 10 min. about 85 per cent of the largest dose but only 25 per cent of the smallest dose had been absorbed. The phenytoin concentration in mucosa and serum increased in an analogous way; maximum values were observed within the first ten minutes. The concentrations in mucosa and serum were dose dependent during the first ten minutes. 0.01 mmol/l and 1 mmol/l phlorizin significantly reduced the transfer of phenytoin (4000 and 2000 mumol/l) from the gut lumen to the mucosa. No inhibition was observed when the initial phenytoin dose was 1000 mumol/l. The results suggest that an active transport mechanism, sensitive to phlorizin, is involved in the intestinal absorption of phenytoin in the rat.
D000818:Animals; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D010672:Phenytoin; D010695:Phlorhizin