Radioimmunoassay and pharmacokinetics of saralasin in the rat and hypertensive patients

A radioimmunoassay for the new angiotensin antagonist, saralasin (1-Sar-8-Ala-angiotensin II), was developed and applied to pharmacologic studies in rats and hypertensive man. Specificity of the assay was established using naturally occurring angiotensins, potential saralasin metabolites, and other synthetic angiotensin analogues. Saralasin pharmacologic half-life of 3.9 min after intravenous administration to rats was similar to the biochemical half-life of 4.2 min. The pharmacologic half-life in high-renin hypertensive patients averaged 8.2 with a biochemical half-life of 3.2 min. These observations suggest that metabolites of saralasin do not accumulate in sufficient quantity in man or rat to interfere with the assay. The biochemical half-life of 3.2 min is consistent with infusion time of less than 20 min required to achieve a stable plasma concentration and pharmacologic activity of saralasin during constant saralasin infusion into hypertensive man. These studies provide a rational basis of future experimental design for saralasin and possibly other peptide analogues.