Pharmacokinetic study of exogenously administered beta-endorphin using a rapid radioreceptor assay in rats.

A rapid radioreceptor assay for measuring beta-endorphin (beta-EP) in unextracted serum has been developed. The method is based upon the inhibition by beta-EP of 3H-naloxone binding to the specific receptors on rat brain membranes, prepared in a stable form of pellets. Effect of serum on the assay was minimized by adding pooled serum to the equal dilution of total serum in the assay mixture. Pharmacokinetic analysis of pharmacologically active beta-EP equivalents (beta-EP eq.) in rats was performed using this method. The serum disappearance of beta-EP eq. after iv administration followed a biexponential decline and pharmacokinetic parameters were calculated by a two-compartment open model. The half-lives of alpha-phase and beta-phase were 2.6 +/- 0.5 min and 6.2 +/- 1.6 hr (mean +/- SE; n = 6), respectively. The volume of the central compartment (V1) and that of steady-state (Vdss) were 67 +/- 16 and 480 +/- 75 ml/kg (mean +/- SE; n = 6), respectively. The total body serum clearance (CLtot) was 2.1 +/- 0.9 ml/min/kg (mean +/- SE; n = 6). The serum disappearance curve of beta-EP eq. obtained in the present study was similar to that previously reported by Houghten et al. (Proc. Natl. Acad. Sci. U.S.A. 77, 4588-4591 (1980) ), in which the disappearance of total radioactivity of tritiated beta-EP in rats was examined.