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Mucosal Uptake of Gabapentin (Neurontin) vs. Pregabalin in the Small Intestine

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Abstract

Purpose. 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°C than at 4°C in the absence of sodium and an additional increase in uptake was observed for pregabalin at 25°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,+.

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REFERENCES

  1. J. S. Bryans and D. J. Wustrow. 3-substituted GABA analogs with central nervous system activity. Med. Res. Rev. 19:149-177 (1999).

    Google Scholar 

  2. M. S. Luer, C. Hamani, M. Dujovny, B. Gidal, M. Cwik, K. Deyo, and J. H. Fischer. Saturable transport of gabapentin at the blood-brain barrier. Neurol. Res. 21:559-562 (1999).

    Google Scholar 

  3. B. H. Stewart, A. R. Kugler, P. R. Thompson, and H. N. Bockbrader. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharm. Res. 10:276-281 (1993).

    Google Scholar 

  4. N. Jezyk, B. H. Stewart, X. Wu, and D. Fleisher. Transport of pregabalin in rat intestine and caco-2 monolayers. Pharm. Res. 16:519-526 (1999).

    Google Scholar 

  5. T. Hatanaka, Y. Nabuchi, and H. Ushio. Transport of N(G)-nitro-L-arginine across intestinal brush border membranes by Na+-dependent and Na+-independent amino acid transporters. Pharm. Res. 16:1770-1774 (1999).

    Google Scholar 

  6. K. O. Vollmer, A. von Hodenberg, and E. U. Kolle. Pharmacokinetics and metabolism of gabapentin in rat, dog and man. Arz.-Forsc. 36:830-839 (1986).

    Google Scholar 

  7. H. Yuasa, G. L. Amidon, and D. Fleisher. Peptide carrier-mediated transport in intestinal brush border membrane vesicles of rats and rabbits: Cephradine uptake and inhibition. Pharm. Res. 10:400-404 (1993).

    Google Scholar 

  8. B. H. Stewart, E. L. Reyner, and R. H. Lu. Gabapentin (Neurontin) transport across Caco-2 cell monolayers: Interactions with zwitterionic and cationic amino acid carriers. Pharm. Res. 11(Suppl)(10):S-254 (1994).

    Google Scholar 

  9. V. Ganapathy, M. E. Ganapathy, and F. H. Leibach. Intestinal transport of peptides and amino acids. In K. E. Barret and M. Donowitz (eds.), Gastrointestinal Transport: Molecular Physiology, Academic Press, San Diego, CA, 2001 pp. 379-412.

    Google Scholar 

  10. G. Rossier, C. Meier, C. Bauch, V. Summa, B. Sordat, F. Verrey, and L. C. Kuhn. LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine. J. Biol. Chem. 274:34948-54 (1999).

    Google Scholar 

  11. D. P. Rajan, R. Kekuda, W. Huang, L. D. Devoe, F. H. Leibach, P. D. Prasad, and V. Ganapathy. Cloning and functional characterization of a Na(+)-independent, broad-specific neutral amino acid transporter from mammalian intestine. Biochim. Biophys. Acta 1463:6-14 (2000).

    Google Scholar 

  12. L. K. Munck and B. G. Munck. Variation in amino acid transport along the rabbit small intestine. Mutual jejunal carriers of leucine and lysine. Biochim. Biophys. Acta 1116:83-90 (1992).

    Google Scholar 

  13. P. Iannoli, J. H. Miller, H. T. Wang, B. Bode, W. W. Souba, N. E. Avissar, and H. C. Sax. Characterization of L-leucine transport system in brush border membranes from human and rabbit small intestine. Metab Clin. Exper. 48:1432-1436 (1999).

    Google Scholar 

  14. T. Hatanaka, Y. Nabuchi, and H. Ushio. Na(+)-dependent and Na(+)-independent transport of L-arginine and L-alanine across dog intestinal brush border membrane vesicles. Comp. Biochem. Physiol. Part B, Biochem. Mol. Biol. 123:105-13 (1999).

    Google Scholar 

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Piyapolrungroj, N., Li, C., Bockbrader, H. et al. Mucosal Uptake of Gabapentin (Neurontin) vs. Pregabalin in the Small Intestine. Pharm Res 18, 1126–1130 (2001). https://doi.org/10.1023/A:1010970809090

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  • DOI: https://doi.org/10.1023/A:1010970809090

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