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 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.
MeSH terms
-
Administration, Oral
-
Amino Acid Sequence
-
Angiotensin-Converting Enzyme Inhibitors / administration & dosage
-
Angiotensin-Converting Enzyme Inhibitors / chemistry
-
Angiotensin-Converting Enzyme Inhibitors / metabolism
-
Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
-
Animals
-
Anti-Bacterial Agents / administration & dosage
-
Anti-Bacterial Agents / chemistry
-
Anti-Bacterial Agents / metabolism
-
Anti-Bacterial Agents / pharmacokinetics
-
Biological Transport
-
Endopeptidases / metabolism*
-
Exopeptidases
-
Humans
-
Hydrolysis
-
Intestinal Mucosa / cytology
-
Intestinal Mucosa / metabolism*
-
Lactams
-
Microvilli / metabolism*
-
Molecular Sequence Data
-
Peptide Hydrolases / metabolism*
-
Peptides / administration & dosage
-
Peptides / chemistry
-
Peptides / metabolism
-
Peptides / pharmacokinetics*
-
Prodrugs / metabolism
Substances
-
Angiotensin-Converting Enzyme Inhibitors
-
Anti-Bacterial Agents
-
Lactams
-
Peptides
-
Prodrugs
-
Endopeptidases
-
Exopeptidases
-
Peptide Hydrolases