Abstract
Pharmacokinetic studies on blood level, tissue distribution and excretion of carvedilol, a new β-blocking agent, were performed in rats during and after the consecutive oral administration of 14C-carvedilol at a daily dose of 10mg/kg for 21 days.
1. The blood radioactivity showed the remarkable accumulation (accumulation factor of 19.0) following the consecutive doses due to the high affinity to the erythrocyte, which was observed only in rats. The plasma concentration of radioactivity reached to the steady state on day 10 and the Css (min) on day 21 was 296ng/ml at the accumulation factor of 4. 1.
2. The radioactivity was well distributed in all the tissues following the consecutive oral doses. The radioactivity in the liver, which was the highest in all of the tissues after a single oral dose, has reached the steady state until day 21 at the accumulation factor of 4.8 in a similar manner as that in the plasma.
The radioactivity in the fat and brown fat increased much greater and disappered much slower than that of plasma.
The remarkable accumulation of radioactivity in spleen was assumed to be ascribed to the high affinity to the erythrocyte.
3. Excretion rates in urine and feces during the consecutive oral doses were nearly constant, and were 3.5 ?? 3.6% and 84.0 ?? 91.6%, respectively. At 48hr after the last dosing, the total excretion into urine and feces was approximately 96% of the dose.
4. The accumulation of radioactivity in tissues was also estimated by whole body autoradiography.
