Comparison of intravenous and nasal bioavailability of clonidine in rodents

Abstract

The bioavailability and cardiac depressant activity of 3H-clonidine was studied following intravenous and nasal administration in rodents. The drug is rapidly absorbed by nasal route, and the peak blood concentration is reached within 10 minutes. The area under the blood concentration-time curve, following intravenous and nasal routes, was found to be 3.55 x 10(5) counts/g/min and 3.75 x 10(5) counts/g/min respectively. The drug was found to eliminate slowly from blood. The t1/2 beta, following intravenous and nasal administration, was found to be 8.8 hr and 8.0 hr respectively. Our electrocardiographic studies, to compare myocardial depression following intravenous and nasal administration of clonidine, revealed that a bolus intravenous clonidine in the dose of 10 micrograms, 30 micrograms, and 100 micrograms/kg body weight produced a significant and transient decrease in heart rate in a dose dependent manner. One rat developed arrhythmia after receiving a higher dose of 100 micrograms/kg body weight of clonidine by intravenous route. However, only a mild decrease in heart rate was observed following nasal administration of clonidine. The examination of the nasal cavity one hour after the single dose of 100 micrograms/kg body weight of clonidine in rats showed no sign of erythema, oedema or lesions. These findings suggest that the nasal route may be a good substitute for I.V. administration of clonidine.