Nasal Delivery of Atenolol and Timolol in the Rat and the Effect of Absorption Enhancers.

Abstract

This study has investigated the nasal mucosa as an alternative site for the administration of atenolol and timolol maleate, two antihypertensive agents whose oral administration is subject to either incomplete absorption (atenolol) or significant first-pass effect (timolol). To this end, the intranasal absorption of these drugs was first evaluated in an in vivo rat model, with and without the absorption enhancers amastatin and sodium glycocholate, and next compared with those obtained after oral and intravenous dosings. Use of the intranasal route resulted in higher plasma drug levels than by the oral route (p < 0.05) and in systemic bioavailabilities that compared very favorably with those obtained intravenously (ca. 90% for both drugs). Bioavailability of the title drugs from the nasal mucosa improved upon coadministration with an absorption enhancer (96-98%, atenolol; ca. 99%, timolol).