The pharmacokinetics and organ distribution of ajmaline and quindine in the mouse

Abstract

After i.v. infusion into mice (lasting 10 s) the time courses of ajmaline and quinidine concentrations in blood, heart, lung, liver, and brain were studied. The drugs were assayed by a spectrofluorophotometric procedure. Blood concentration data obtained were fitted graphically and calculations were performed in accordance with an open two compartment model. Blood kinetic data were very similar for both alkaloids. A rapid distribution phase with a t0.5alpha of 3.0 min for ajmaline and 2.5 min for quindine was followed by a disposition phase with a t0.5beta of 16 min for ajmaline and 20 min for quinidine. High tissue accumulation of both alkaloids was found in lung, liver, and heart and this is also reflected by the volume of distribution Vdbeta, which was 136 ml for ajmaline and 116 ml for quinidine (body weight of the mice = 31 g). With equilibrium dialysis a 62% binding of ajmaline and a 77% binding of quinidine to mouse blood constituents was found. Both drugs were highly metabolized since only 5% of a given dose was excreted unchanged in the urine.