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Structural Specificity of Mucosal-Cell Transport and Metabolism of Peptide Drugs: Implication for Oral Peptide Drug Delivery

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Abstract

The brush border membrane of intestinal mucosal cells contains a peptide carrier system with rather broad substrate specificity and various endo- and exopeptidase activities. Small peptide (di-/ tripeptide)-type drugs with or without an N-terminal α-amino group, including β-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors, are transported by the peptide transporter. Poly-peptide drugs are hydrolyzed by brush border membrane proteolytic enzymes to di-/tripeptides and amino acids. Therefore, while the intestinal brush border membrane has a carrier system facilitating the absorption of di-/tripeptide drugs, it is a major barrier limiting oral availability of polypeptide drugs. In this paper, the specificity of peptide transport and metabolism in the intestinal brush border membrane is reviewed.

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  1. College of Pharmacy, University of Minnesota, 308 Harvard Street S.E., Minneapolis, Minnesota, 55455

    Jane P. F. Bai

  2. College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109-1065

    Gordon L. Amidon

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Bai, J.P.F., Amidon, G.L. Structural Specificity of Mucosal-Cell Transport and Metabolism of Peptide Drugs: Implication for Oral Peptide Drug Delivery. Pharm Res 9, 969–978 (1992). https://doi.org/10.1023/A:1015885823793

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