CONTRASTING NUTRIENT EFFECTS ON THE PLASMA-LEVELS OF AN AMINO ACID-LIKE ANTIEPILEPTIC AGENT FROM JEJUNAL ADMINISTRATION IN DOGS

The absorption of gabapentin was investigated by monitoring drug plasm a levels as a function of time following midjejunal administration in mongrel dogs. From previous work, dose-dependent absorption had. been postulated to be a consequence of carrier mediated transport and a par acellular pathway had been postulated to contribute to the passive abs orption component in mammalian small intestine, The potential for amin o acid inhibition of the carrier-mediated absorption component was inv estigated by drug coinfusion with leucine and phenylalanine. The poten tial for monosaccharide-enhanced increases in drug absorption was stud ied by drug coinfusion with D-glucose and 3-O-methylglucose. While low er drug plasma levels were observed with amino acid coinfusion Versus controls in each of the dogs studied, mean area under the plasma level time curves (AUC) were not statistically significantly different (p l ess than or equal to 0.07). Monosaccharide coinfusion significantly in creased gabapentin AUC over control studies (p less than or equal to 0 .014) and over coinfusion with L-system amino acids (p less than or eq ual to 0.0025). Implications for the mechanisms of intestinal absorpti on of this amino acid-like antiepileptic drug in this canine model are discussed.