Disposition and metabolism of [14C]cadralazine in rats (I) Single administration

Absorption, distribution, excretion and metabolism of [14C]cadralazine were studied in normal male, and pregnant and lactating female rats after oral and/or intravenous administration at the dose of 3 mg/kg. 1. Cadralazine was found to be absorbed from the whole region of small intestine as it was shown in rats with ligations at the bile duct, pylorus and lower end of duodenum. 2. Plasma levels of radioactivity reached the maximum of about 1 μg eq./ml at 1 hr aftdr oral administration in normal rats and decreased with the half life of 1.8 hr. The ratio for AUC after oral/intravenous administration was around 0.9. 3. Drug concentrotion in most tissues reached the maximum at 1 hr after oral administration. The highest concentrotions were in kidrey and liver, most other tissue levels including the target aorta were virtually close to plasma level and brain level was the lowest. The rate of disappearance of radioactivity was slightly slower in some tissues such as aorta than that in plasma. 4. The level of radioactivity in fetus was lower than maternal plasma level. The level in the milk was slightly higher than in plasma. 5. The extent of protein binding was as low as about 20%. 6. About 86 % of orally administered radioactivity was excreted in the urine within 96 hr, and 6 % in the bile within 48 hr. The ratio of urinary excretions after oral/intravenous administration was about 0.9. 7. Major radioactive compound found in plasma and urine was the unchanged cadralazine. A few metabolites, including known ones, were found to be minor.