PHARMACOKINETIC CHARACTERIZATION OF THE POSTDISTRIBUTION PHASE OF PROHORMONE ATRIAL NATRIURETIC PEPTIDES AMINO-ACIDS 1-98, 31-67, AND ATRIAL-NATRIURETIC-FACTOR DURING AND AFTER RAPID RIGHT VENTRICULAR PACING IN DOGS

Release rate constants and disappearance rate constants were determined for three atrial natriuretic peptides consisting of amino acids 1-98 (i.e., proANF 1-98), the midportion of he ANF prohormone consisting of amino acids 31-67 (i.e., proANF 31-67) and amino acids 99-126 (i.e., ANF) after right ventricular pacing at 100, 125, 150, and 180 bpm in six male mongrel dogs. Right atrial and femoral vein blood was obtained at baseline, and at 5, 12, 19, 26, 56, 86, 116, 146, and 206 minutes after right ventricular pacing. Resulting plasma concentration-time data derived parameters were compared. The disappearance rate constants for atrial and femoral venous proANF 1-98 were 0.0144 +/- 0.0087 (X +/- SD) and 0.0175 +/- 0.0075 min-1, respectively (t = 0.6158) and release rate constants were 0.1569 +/- 0.1504 and 0.0670 +/- 0.0393 min-1, respectively (t = 1.8269; P > .05). The proANF 31-67 disappearance rate constants were 0.0139 +/- 0.0082 and 0.0148 +/- 0.0132 min-1, respectively (t = 0.1192) and release rate constants were 0.0957 +/- 0.0414 and 0.1984 +/- 0.1762 min-1, respectively (t = 1.4812). The ANF elimination phase disappearance rate constants were 0.0663 +/- 0.0273 and 0.1116 +/- 0.0539 min-1 (t = 2.0923, P > .05), respectively, and the release rate constants were 0.1335 +/- 0.0532 and 0.1638 +/- 0.0520 min-1 (t = 0.7878, P > .05), respectively. These data indicate that proANF 1-98 and proANF 31-67 circulating beta-post-distribution half-lives are approximately 45 minutes whereas beta-half-life of ANF is 10 minutes. Persisting concentrations of proANF 1-98 and proANF 31-67 in plasma may better explain the proported sustained pharmacologic effects that have been attributed to ANF, which has a mean alpha distribution phase half-life of 3.5 minutes and a beta half-life of 10 minutes.