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. 1993 Mar;35(3):243–250. doi: 10.1111/j.1365-2125.1993.tb05691.x

The effect of L-leucine on the absorption of levodopa, studied by regional jejunal perfusion in man.

H Lennernäs 1, D Nilsson 1, S M Aquilonius 1, O Ahrenstedt 1, L Knutson 1, L K Paalzow 1
PMCID: PMC1381569  PMID: 8471400

Abstract

1. A new method for perfusing a 10 cm segment of jejunum in humans has been used in seven subjects to study the effect of the amino acid L-leucine (40 mM) on the intestinal absorption of levodopa (2.5 mM). The tube contains six channels and has two inflatable balloons, which enable a perfusion of a closed and defined segment of the proximal small intestine. 2. L-leucine decreased the intestinal absorption of levodopa from 40 +/- 19 to 21 +/- 15% but was without effect on the absorption of antipyrine, benserazide and D-glucose. 3. We confirm that levodopa is absorbed by the active transport system normally responsible for the absorption of large neutral amino acids (LNAA) in humans. Oral absorption by passive diffusion, probably by the paracellular route, might also occur for levodopa in the proximal part of the small intestine.

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Selected References

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  1. Adibi S. A., Mercer D. W. Protein digestion in human intestine as reflected in luminal, mucosal, and plasma amino acid concentrations after meals. J Clin Invest. 1973 Jul;52(7):1586–1594. doi: 10.1172/JCI107335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amidon G. L., Kou J., Elliott R. L., Lightfoot E. N. Analysis of models for determining intestinal wall permeabilities. J Pharm Sci. 1980 Dec;69(12):1369–1373. doi: 10.1002/jps.2600691204. [DOI] [PubMed] [Google Scholar]
  3. Amidon G. L., Merfeld A. E., Dressman J. B. Concentration and pH dependency of alpha-methyldopa absorption in rat intestine. J Pharm Pharmacol. 1986 May;38(5):363–368. doi: 10.1111/j.2042-7158.1986.tb04588.x. [DOI] [PubMed] [Google Scholar]
  4. Bergmark J., Carlsson A., Granerus A. K., Jagenburg R., Magnusson T., Svanborg A. Decarboxylation of orally administered L-dopa in the human digestive tract. Naunyn Schmiedebergs Arch Pharmacol. 1972;272(4):437–440. doi: 10.1007/BF00501249. [DOI] [PubMed] [Google Scholar]
  5. Eichelbaum M., Ochs H. R., Roberts G., Somogyi A. Pharmacokinetics and metabolism of antipyrine (phenazone) after intravenous and oral administration. Arzneimittelforschung. 1982;32(5):575–578. [PubMed] [Google Scholar]
  6. Eisler T., Eng N., Plotkin C., Calne D. B. Absorption of levodopa after rectal administration. Neurology. 1981 Feb;31(2):215–217. doi: 10.1212/wnl.31.2.215. [DOI] [PubMed] [Google Scholar]
  7. Frankel J. P., Kempster P. A., Bovingdon M., Webster R., Lees A. J., Stern G. M. The effects of oral protein on the absorption of intraduodenal levodopa and motor performance. J Neurol Neurosurg Psychiatry. 1989 Sep;52(9):1063–1067. doi: 10.1136/jnnp.52.9.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hidalgo I. J., Borchardt R. T. Transport of a large neutral amino acid (phenylalanine) in a human intestinal epithelial cell line: Caco-2. Biochim Biophys Acta. 1990 Sep 21;1028(1):25–30. doi: 10.1016/0005-2736(90)90261-l. [DOI] [PubMed] [Google Scholar]
  9. Hu M., Amidon G. L. Passive and carrier-mediated intestinal absorption components of captopril. J Pharm Sci. 1988 Dec;77(12):1007–1011. doi: 10.1002/jps.2600771204. [DOI] [PubMed] [Google Scholar]
  10. Iga K., Ogawa Y., Yashiki T., Shimamoto T. Estimation of drug absorption rates using a deconvolution method with nonequal sampling times. J Pharmacokinet Biopharm. 1986 Apr;14(2):213–225. doi: 10.1007/BF01065261. [DOI] [PubMed] [Google Scholar]
  11. Ishimitsu T., Hirose S. Simultaneous assay of 3,4-dihydroxyphenylalanine, catecholamines and O-methylated metabolites in human plasma using high-performance liquid chromatography. J Chromatogr. 1985 Feb 8;337(2):239–248. doi: 10.1016/0378-4347(85)80037-2. [DOI] [PubMed] [Google Scholar]
  12. Jobin G., Cortot A., Godbillon J., Duval M., Schoeller J. P., Hirtz J., Bernier J. J. Investigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in the stomach, duodenum and jejunum. Br J Clin Pharmacol. 1985;19 (Suppl 2):97S–105S. doi: 10.1111/j.1365-2125.1985.tb02749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kerlin P., Zinsmeister A., Phillips S. Relationship of motility to flow of contents in the human small intestine. Gastroenterology. 1982 Apr;82(4):701–706. [PubMed] [Google Scholar]
  14. Knutson L., Odlind B., Hällgren R. A new technique for segmental jejunal perfusion in man. Am J Gastroenterol. 1989 Oct;84(10):1278–1284. [PubMed] [Google Scholar]
  15. Lennernäs H., Ahrenstedt O., Hällgren R., Knutson L., Ryde M., Paalzow L. K. Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man. Pharm Res. 1992 Oct;9(10):1243–1251. doi: 10.1023/a:1015888813741. [DOI] [PubMed] [Google Scholar]
  16. Merfeld A. E., Mlodozeniec A. R., Cortese M. A., Rhodes J. B., Dressman J. B., Admidon G. L. The effect of pH and concentration on alpha-methyldopa absorption in man. J Pharm Pharmacol. 1986 Nov;38(11):815–822. doi: 10.1111/j.2042-7158.1986.tb04501.x. [DOI] [PubMed] [Google Scholar]
  17. Ochsenfahrt H., Winne D. The contribution of solvent drag to the intestinal absorption of the basic drugs amidopyrine and antipyrine from the jejunum of the rat. Naunyn Schmiedebergs Arch Pharmacol. 1974;281(2):175–196. doi: 10.1007/BF00503497. [DOI] [PubMed] [Google Scholar]
  18. Pappenheimer J. R., Reiss K. Z. Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J Membr Biol. 1987;100(2):123–136. doi: 10.1007/BF02209145. [DOI] [PubMed] [Google Scholar]
  19. Riley D., Lang A. E. Practical application of a low-protein diet for Parkinson's disease. Neurology. 1988 Jul;38(7):1026–1031. doi: 10.1212/wnl.38.7.1026. [DOI] [PubMed] [Google Scholar]
  20. Robertson D. R., Higginson I., Macklin B. S., Renwick A. G., Waller D. G., George C. F. The influence of protein containing meals on the pharmacokinetics of levodopa in healthy volunteers. Br J Clin Pharmacol. 1991 Apr;31(4):413–417. doi: 10.1111/j.1365-2125.1991.tb05555.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Robertson D. R., Renwick A. G., Wood N. D., Cross N., Macklin B. S., Fleming J. S., Waller D. G., George C. F. The influence of levodopa on gastric emptying in man. Br J Clin Pharmacol. 1990 Jan;29(1):47–53. doi: 10.1111/j.1365-2125.1990.tb03601.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sarkar M. A., Karnes H. T. Comparison of solid-phase extraction and liquid-liquid extraction for high-performance liquid chromatographic analysis of antipyrine in plasma. J Chromatogr. 1988 Dec 29;434(1):324–326. doi: 10.1016/0378-4347(88)80096-3. [DOI] [PubMed] [Google Scholar]
  23. Tsui J. K., Ross S., Poulin K., Douglas J., Postnikoff D., Calne S., Woodward W., Calne D. B. The effect of dietary protein on the efficacy of L-dopa: a double-blind study. Neurology. 1989 Apr;39(4):549–552. doi: 10.1212/wnl.39.4.549. [DOI] [PubMed] [Google Scholar]
  24. Wade D. N., Mearrick P. T., Morris J. L. Active transport of L-dopa in the intestine. Nature. 1973 Apr 13;242(5398):463–465. doi: 10.1038/242463a0. [DOI] [PubMed] [Google Scholar]
  25. Wade L. A., Katzman R. Synthetic amino acids and the nature of L-DOPA transport at the blood-brain barrier. J Neurochem. 1975 Dec;25(6):837–842. doi: 10.1111/j.1471-4159.1975.tb04415.x. [DOI] [PubMed] [Google Scholar]
  26. Yeh K. C., August T. F., Bush D. F., Lasseter K. C., Musson D. G., Schwartz S., Smith M. E., Titus D. C. Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. Neurology. 1989 Nov;39(11 Suppl 2):25–38. [PubMed] [Google Scholar]

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