Intranasal administration of different liquid formulations of bumetanide to rabbits

The bioavailability of bumetanide in rabbits after intranasal administratio n of eight formulations intended for use in acute situations has been studi ed. The vehicles tested were combinations of phosphate buffer, pH 7.4, glyc ofurol 75, polyethylene glycol 200 and coconut oil. A mixture of 5% glycofu rol in polyethylene glycol 200 was administered containing doses of 1 and 8 mg bumetanide respectively. For all other formulations the lower dose leve l only was studied. The t(max) obtained ranged from 3 to 10 min. The vehicl es resulting in the highest rate of absorption were 60% glycofurol in cocon ut oil and pure glycofurol. The observed bioavailability for the different formulations ranged from 16 to 37% for the time period 0-120 min. The bioav ailability was also calculated omitting the initial peak seen after i.v. in jection, which may be undesirable. Using this method bioavailabilities of 3 3-82% for the time interval 5-120 min was found. The study also demonstrate d that the total amount of bumetanide absorbed increased proportionally to the dose administered. The rate of absorption of bumetanide from all formul ations tested may be relevant for the treatment of acute oedematous states. The t(max) obtained after intranasal administration was shorter than repor ted for other non-parenteral routes of administration. (C) 2000 Elsevier Sc ience B.V. All rights reserved.