Pharmacokinetics of the vasopressin antagonist, SK and F 101926, a synthetic octapeptide, in the rat

SK and F 101926 is a synthetic analogue of vasopressin which antagonizes vasopressin induced antidiuresis. Radiolabeled SK and F 101926 (3H-3,3-D-TYR) was administered i.v. as a single bolus to male Sprague Dawley rats. Serial plasma samples were analyzed for SK and F 101926 by HPLC/LSC. The plasma concentration time curve for SK and F 101926 displayed three disposition phases. However, 80% of the total area under the curve was represented in one phase which displayed a half-life (t 1/2) of 20 min. The total systematic clearance (Cl) and the steady state volume of distribution (Vdss) were 15 ml/min/kg and 450 ml/kg, respectively. The t 1/2, Cl and Vdss were identical following doses of 10 and 100 μg/kg. 3H-SK and F 101926 accounted for > 80% of the plasma radiolabel 0-30 min after dosing. However, by 12 hr, 3H-SK and F 101926 represented only 6% of the plasma radiolabel. Following oral administration of 3H-SK and F 101926, < 5% of the administered radiolabel reached the systematic circulation; however, no parent compound was detectable in plasma. These studies demonstrate that although SK and F 101926 has a relatively low systematic clearance, it also displays a relatively small volume of distribution which together result in a moderate beta elimination half-life