Characterization of the intestinal transport parameters for small peptide drugs

Abstract

Several laboratories have recently shown that many peptides and peptide-similar drugs are well absorbed in the mammalian intestine via the peptide transport system for nutrient small peptide (dipeptides and tripeptides) absorption. This facilitated non-passive transport in the intestine is saturable and concentration dependent, and further characterized by the mutual inhibition of transport among the compounds. Peptide and peptide derivative drugs are often zwitterionic compounds, generally ionized at the intestinal pH and therefore are expected to undergo only limited passive absorption. Nonpassive and passive transport are independent and may occur simultaneously. Peptide drugs that have been shown to be transported by the peptide carrier systems are various [beta]-lactams, the angiotensin converting enzyme (ACE) inhibitors captopril, enalapril, lisinopril and SQ 29,852, TRH and its analogues, and alafosfaline and some of its analogues. The carrier characterization is based upon transport parameters, Km Jmax (or Vmax) and Pc (Michaelis-Menten constant, maximal flux and the carrier permeability constant respectively) determined over the last years for several dipeptides, [beta]-lactam antibiotics and ACE inhibitors.