Radioimmunoassay for ceronapril, a new angiotensin-converting enzyme inhibitor, and its application to a pharmacokinetic study in healthy male volunteers

Abstract

Ceronapril is a member of a new chemical class of angiotensin-converting enzyme inhibitors being developed by The Bristol-Myers Squibb Pharmaceutical Research Institute. A radioimmunoassay (RIA) has been developed for the measurement of ceronapril in biological fluids. The RIA has a range of 0 to 500 ng/ml and has the sensitivity to detect 1.0 ng/ml of ceronapril. Satisfactory zero binding and sensitivity were obtained after a 2-h incubation at room temperature or overnight at 4 degrees C. Separation of the antibody-bound and free radiolabel was achieved by employing polyethylene glycol-goat anti-rabbit gamma-globulin separant. A quantitative recovery of the exogenous analyte was obtained at all concentrations of ceronapril tested. Intraassay coefficients of variance (CV's) were 3.9% and 4.6% for the low and medium controls, respectively. A highly significant statistical correlation between RIA and [14C]TLRC was observed for both plasma and urine samples. Clinical samples from the ascending dosage studies have been analyzed by the ceronapril RIA. The maximum concentration and the area under the plasma concentration-time curve did not increase in a dose-proportional manner for doses above 100 mg.