Disposition and metabolism of [¹⁴C]cadralazine in rats (II) Repeated administration

Abstract

Absorption, distribution, excretion and metabolism of [¹⁴C]cadralazine were studied in rats after 10 consecutive daily oral administration at the dose of 3 mg/kg.
1. Plasma levels at 1 hr after each administration were around 1 μg eq./ml. Levels after the last administration decreased biphasically with half lives of 2.4 and 12.5 hr.
2. At 1 hr after the last administration, drug concentration in erythrocyte was elevated 2.7 times in comparison to that after single administration but other tissue levels were virtually similar to those after single administration. At 24 hr, erythrocyte and liver levels were higher.
3. Urinary and fecal excretion amounted to about 93 and 8 % of administered radioactivity during and after repeated administration.
4. Composition of plasma and urinary metabolites was virtually similar to that after single administration and the unchanged cadralazine was the major component.