Studies on Heart. XXIII. Distribution of [1-14C] Acetamidino-antiarrhythmic Peptide (14C-AAP) in Mice

The distribution of [1-14C] acetamidino-antiarrhythmic peptide (14C-AAP) in mice was studied by direct counting and whole-body autoradiography. Intravenously injected 14C decreased rapidly in blood during 1 to 20 min and gradually during 20 to 180 min. At 180 min 68% of the radioactivity had appeared in the urine. At 60 min unmetabolized 14C-AAP was present in the urine. At 1 min the radioactivity was highest in the kidney, followed by the lung, liver, and myocardium in that order. Radioactivity increased in the kidney and myocardium during 1 to 6 min, while the radioactivity in the lung and liver decreased rapidly from 1 to 60 min. Autoradiograms revealed that at 6 min after injection (i.v.) the highest radioactivities were seen in the kidney, urine, heart, lung, submaxillary gland, bone and gut wall. No radioactivity was present in the brain, spinal cord, gut contents or fetus. At 20 to 60 min the radioactivity levels in the organs were much less than those seen at 6 min, except for the kidney and urine. In mice orally given 14C-AAP, the maximum plateau levels of radioactivity were found in the myocardium (0.04% of dose) and blood (2.5%) at 40 to 120 min. In serum at 60 min, 14C-AAP was still present in the original molecular form, unbound to macromolecules. Thus, 14C-AAP accumulates in the myocardium of the target organ for a short time immediately after injection (i.v.), corresponding to the period of the QTc interval prolongation by AAP. 14C-AAP does not accumulate for long in any organ except for the kidney, and is largely excreted in urine within 60 min.