[¹⁴C]cadralazine: absorption, distribution and excretion in rat and dog

Summary

Absorption, distribution and excretion of [¹⁴C]cadralazine in rat after oral and i.v. administration of 3 mg/kg were studied. Plasma levels after oral administration of 10 and 45 mg/kg were also evaluated. A direct relation between dose and plasma levels was demonstrated. The drug was well absorbed, disappeared very rapidly from plasma, and was distributed in all the organs examined, with the highest concentration in liver, kidney, and gastrointestinal tract. For more than 4 days excretion was essentially through the urine (75.6% after i.v. and 80% after oral administration), whereas faecal and biliary excretions were quite low. The total recovery was respectively 77.6% and 83.2% after i.v. and oral administration of 3 mg/kg, with the greatest amount (65–70% of the administered dose) appearing in the first 4 to 7 hours. Placental transfer and excretion of radioactivity with milk were demonstrated. Drug-protein binding was 25.9%. Elimination of¹⁴CO₂ was not observed. Plasma levels in dog, after oral and i.v. administration of 1 mg/kg of labelled compound, showed similar behaviour to that observed in the rat. Binding of the radioactivity to erythrocytes was found; the radioactivity values observed up to 24 hours were constant with time and not dependent on the decreasing plasma levels. The total recovery (urine and faeces) in the dog over 4 days was 71.1% and 82.1% after oral and i.v. dose, respectively. Preliminary metabolic approaches in rats showed that cadralazine was essentially excreted as unchanged drug in the presence of minor metabolites.