Mucosal uptake of gabapentin (neurontin) vs. pregabalin in the small intestine.
OBJECTIVE
To compare the mucosal membrane transport of gabapentin and pregabalin in animal small intestine.


METHODS
Uptake of the two drugs by brush-border membrane vesicles (BBMV) from rat and rabbit small intestine was studied as a function of temperature, uptake-medium sodium content, and intestinal region. Amino acid inhibition studies were conducted with pregabalin.


RESULTS
Gabapentin uptake by rat and rabbit jejunal BBMV was sodium independent, whereas pregabalin uptake was sodium dependent. Uptake of both drugs in rabbit small intestinal vesicles was greater at 25 degrees C than at 4 degrees C in the absence of sodium and an additional increase in uptake was observed for pregabalin at 25 degrees C in the presence of sodium. Pregabalin uptake in rabbit duodenal, jejunal, and ileal BBMV was equivalent, whereas gabapentin uptake was greater in duodenal and ileal BBMV, compared with jejunal BBMV. Although inhibition is weak, a decrease in BBMV uptake of pregabalin is observed with coincubation of high concentrations of both neutral and basic amino acids.


CONCLUSIONS
Amino acid carriers mediate the apical uptake of both drugs in the small intestine. Although gabapentin and pregabalin are structurally similar, their small intestinal mucosal uptake differs in sodium dependence and region dependence. Gabapentin uptake is likely mediated by system b0,+, whereas pregabalin uptake is also mediated by B0 and/or B0,+.
Piyapolrungroj
N
N
Faculty of Pharmacy, Silpakorn University, Nakorn-pathom, Thailand.
Li
C
C
Bockbrader
H
H
Liu
G
G
Fleisher
D
D
D000085:Acetates / Q000493:pharmacokinetics*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000588:Amines; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008871:Microvilli / Q000201:enzymology / Q000378:metabolism; D000069583:Pregabalin; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
D000085:Acetates; D000588:Amines; D000596:Amino Acids; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D012964:Sodium; D000469:Alkaline Phosphatase