Relative inhibitory potency and plasma drug levels of angiotensin converting enzyme inhibitors in the rat.

Abstract

1. 125I-351A, a tyrosyl derivative of the angiotensin converting enzyme (ACE) inhibitor lisinopril, was used as a radioligand, and radioinhibitor binding and displacement assays have been established. 2. The in vitro potency of a range of ACE inhibitors against rat ACE was determined using the radioinhibitor binding displacement assay. 3. The concentration of an ACE inhibitor needed to displace 50% of 125I-351A bound to rat ACE (ID50) was closely correlated with the concentration needed to inhibit 50% of ACE enzymatic activity (IC50). 4. Radioinhibitor binding displacement assay was used to measure the plasma concentrations of lisinopril, cilazapril and perindopril in rat plasma. 5. Plasma concentrations of lisinopril measured by radioimmunoassay were identical with that measured by radioinhibitor binding assays.