Mucosal uptake of gabapentin (Neurontin) vs. Pregabalin in the small intestine

Purpose. To compare the mucosal membrane transport of gabapentin and pregab alin in animal small intestine. Methods. Uptake of the two drugs by brush-border membrane vesicles (BBMV) f rom rat and rabbit small intestine was studied as a function of temperature , uptake-medium sodium content, and intestinal region. Amino acid inhibitio n studies were conducted with pregabalin. Results. Gabapentin uptake by rat and rabbit jejunal BBMV was sodium indepe ndent, whereas pregabalin uptake was sodium dependent. Uptake of both drugs in rabbit small intestinal vesicles was greater at 25 degreesC than at 4 d egreesC in the absence of sodium and an additional increase in uptake was o bserved for pregabalin at 25 degreesC 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 je junal BBMV. Although inhibition is weak, a decrease in BBMV uptake of prega balin 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 s imilar, their small intestinal mucosal uptake differs in sodium dependence and region dependence. Gabapentin uptake is likely mediated by system b(0.), whereas pregabalin uptake is also mediated by B-0 and/or B0.+.