Aminozolamide suspension: the role of the vehicle in a topical carbonic anhydrase inhibitor.

Aminozolamide (6-amino-2-benzothiazolesulfonamide) is a carbonic anhydrase inhibitor derived from ethoxzolamide that has been shown in gel formulation to lower IOP in rabbits, primates and humans. This study was designed to determine whether aminozolamide in suspension was also effective in lowering IOP. In separate single dose and multiple dose studies, patients with ocular hypertension were tested over 24 hours. No statistically significant drop in intraocular pressure was noted between the treated and control eye. In addition, conjunctival injection was noted in three of eleven subjects after multiple dosing. These studies suggest that retention of aminozolamide at the active site is inadequate when delivered in a suspension vehicle. In the past 10 years, efforts to develop an effective topical carbonic anhydrase inhibitor have been vigorously pursued. This has been aided by advancements in drug delivery and chemical synthesis involving molecular modification of existing carbonic anhydrase inhibitors. Various compounds have been developed that retain carbonic anhydrase inhibitory activity, penetrate the cornea and optimize the other important pharmacokinetic properties to lower intraocular pressure. One such compound, aminozolamide (6-amino-2-benzothiazolesulfonamide) is derived from ethoxzolamide. In suspension, it has been shown to lower IOP in rabbits and primates. It also has been shown to lower IOP in patients with ocular hypertension when delivered in a gel vehicle. The carbomer gel vehicle, a drug delivery system also used with pilocarpine (Pilopine HS), is used to prolong ocular contact and enhance penetration. The importance of the role of the vehicle in a topical carbonic anhydrase inhibitor has not been assessed.(ABSTRACT TRUNCATED AT 250 WORDS)