Structural specificity of mucosal-cell transport and metabolism of peptide drugs: implication for oral peptide drug delivery.
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 alpha-amino group, including beta-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors, are transported by the peptide transporter. Polypeptide 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.
Bai
J P
JP
University of Minnesota, College of Pharmacy, Minneapolis 55455.
Amidon
G L
GL
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001692:Biological Transport; D010450:Endopeptidases / Q000378:metabolism*; D020689:Exopeptidases; D006801:Humans; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007769:Lactams; D008871:Microvilli / Q000378:metabolism*; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000900:Anti-Bacterial Agents; D007769:Lactams; D010455:Peptides; D011355:Prodrugs; D010450:Endopeptidases; D020689:Exopeptidases; D010447:Peptide Hydrolases