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...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1997-08, Vol.86 (8), p.953-957
Main Authors: Stevenson, Cheryl M., Radulovic, Louis L., Bockbrader, Howard N., Fleisher, David
Format: Article
Language:English
Subjects:
Acetates - administration & dosage
Acetates - blood
Amines
Animals
Anticonvulsants - administration & dosage
Anticonvulsants - blood
Anticonvulsants. Antiepileptics. Antiparkinson agents
Area Under Curve
Biological and medical sciences
Cyclohexanecarboxylic Acids
Diet
Dogs
Female
Food-Drug Interactions
gamma-Aminobutyric Acid
Intestinal Absorption
Jejunum
Male
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
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Summary: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 ≤ 0.07). Monosaccharide coinfusion significantly increased gabapentin AUC over control studies (p≤0.014) and over coinfusion with L-system amino acids (p≤0.0025). Implications for the mechanisms of intestinal absorption of this amino acid-like antiepileptic drug in this canine model are discussed.
ISSN:0022-3549
1520-6017
DOI:10.1021/js9603360