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 plasma 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 paracellular pathway had been postulated to contribute to the passive absorption component in mammalian small intestine. The potential for amino acid inhibition of the carrier-mediated absorption component was investigated by drug coinfusion with leucine and phenylalanine. The potential for monosaccharide-enhanced increases in drug absorption was studied by drug coinfusion with D-glucose and 3-O-methylglucose. While lower 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 < or = 0.07). Monosaccharide coinfusion significantly increased gabapentin AUC over control studies (p < or = 0.014) and over coinfusion with L-system amino acids (p < or = 0.0025). Implications for the mechanisms of intestinal absorption of this amino acid-like antiepileptic drug in this canine model are discussed.
Stevenson
C M
CM
Pharmaceutical Research & Development, Whitehall-Robins Health Care, Hammonton, NJ 08037, USA.
Radulovic
L L
LL
Bockbrader
H N
HN
Fleisher
D
D
D000085:Acetates / Q000008:administration & dosage / Q000097:blood*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood*; D019540:Area Under Curve; D003509:Cyclohexanecarboxylic Acids; D004032:Diet; D004285:Dogs; D005260:Female; D018565:Food-Drug Interactions; D000077206:Gabapentin; D007408:Intestinal Absorption; D007583:Jejunum; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin