Cardiovascular effects and pharmacokinetics of the carboxylic ionophore monensin in dogs and rabbits

Monensin, a carboxylic ionophore, produces strong pressor, positive chronotropic effects and elevates the blood glucose level when injected intravenously (100 μg/kg) into pentobarbital anesthetized dogs or administered orally (2 mg/kg) to conscious dogs. Intravenously administered monensin disappeared from the blood rapidly with a $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ of ca. 2.5 min and, in the conscious dogs, ingested monensin showed a peak plasma level 90 min after feeding; this coincided with the time of maximum increase in arterial blood pressure and blood glucose. In conscious rabbits, although higher doses of monensin were administered, 200 μg/kg intravenously and 10 mg/kg orally, its cardiovascular effects were less than observed in the dog and were slower in onset. This correlated with slower clearing of injected monensin from the blood ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{= 8}\text{min}$) and slower entry of ingested monensin from the gut into the blood. Rabbit plasma and tissue levels were higher 17 hr after oral ingestion of monensin than six hr after ingestion.