Transport of Angiotensin-Converting Enzyme Inhibitors by H/Peptide Transporters Revisited

Abstract

Angiotensin-converting enzyme (ACE) inhibitors are often re-garded as substrates for the H/peptide transporters (PEPT)1 and PEPT2. Even though the conclusions drawn from pub-lished data are quite inconsistent, in most review articles PEPT1 is claimed to mediate the intestinal absorption of ACE inhibitors and thus to determine their oral availability. We sys-tematically investigated the interaction of a series of ACE in-hibitors with PEPT1 and PEPT2. First, we studied the effect of 14 ACE inhibitors including new drugs on the uptake of the dipeptide [14C]glycylsarcosine into human intestinal Caco-2 cells constitutively expressing PEPT1 and rat renal SKPT cells expressing PEPT2. In a second approach, the interaction of ACE inhibitors with heterologously expressed human PEPT1 and PEPT2 was determined. In both assay systems, zofenopri