Studies on the metabolic fate of carvedilol. (I). Pharmacokinetics in rat following a single oral dose.

Pharmacokinetic studies on time-course of blood levels, tissue distribution and excretion of carvedilol, a new β-blocking agent, were performed in rats after a single oral administration of 14C-carvedilol at a dose of 10mg/kg.1. The blood concentration of radioactivity showed the remarkable retention due to the high affinity to the erythrocyte, which has been observed only in rats until now.The plasma concentration of radioactivity reached the Cmax of 713ng/ml(carvedilol equivalent) at lhr and decreased with relatively long half-life of 29.8hr.2. The radioactivity was relatively well distributed in all the tissues, especially in liver, gastro-intestinal tissues, kidney, harderian gland, lung, hypophysis, submaxillary gland and pancreas. The concentrations in these tissues were 2 ?? 10 times higher than that in the plasma. The concentrations in the other tissues were lower than that in the plasma. The radioactivity in most tissues, except erythrocyte and harderian gland, disappeared in a similar manner as that in the plasma. 3. The radioactivity was excreted during 72hr into urine and feces at the rate of 4.5 and 90.8% of the dose, respectively. The most part of fecal excretion was assumed to be ascribed to biliary excretion.4. The pharmacokinetic profile of carvedilol was also estimated by whole body autoradiography.