Structural specificity of mucosal-cell transport and metabolism of peptide drugs: implication for oral peptide drug delivery

• Published in: Pharmaceutical research 1992-08, Vol.9 (8), p.969-978
• Main Authors: Bai, J. P., Amidon, G. L.
• Format: Article
• Language: English
• Subjects: 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 and medical sciences; Biological Transport; Endopeptidases - metabolism; Exopeptidases; General pharmacology; Humans; Hydrolysis; Intestinal Mucosa - cytology; Intestinal Mucosa - metabolism; Lactams; Life Sciences (General); Medical sciences; Microvilli - metabolism; Molecular Sequence Data; Peptide Hydrolases - metabolism; Peptides - administration & dosage; Peptides - chemistry; Peptides - metabolism; Peptides - pharmacokinetics; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Prodrugs - metabolism; Space life sciences
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/a:1015885823793

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.