Intraocular pressure-lowering activity and in vivo disposition of dipivalyl terbutalone in rabbits

The ocular hypotensive activity and in vivo disposition of dipivalyl terbut alone, a chemical delivery system for terbutaline, were investigated in the albino rabbit model. The dose-response relationship was assessed at drug c oncentrations ranging from 0.5 to 4% in normal saline. Intraocular pressure (IOP)-lowering activity of dipivalyl terbutalone was compared with epineph rine in equal concentrations. The in vivo disposition was investigated afte r topical administration of dipivalyl terbutalone at 4% dose level for whic h two metabolic products, terbutaline, and terbutalone, were monitored in d ifferent anterior segment tissues/fluid of albino rabbits, including cornea l and iris-ciliary body homogenates and aqueous humor. the instillation of 0.5, 1, 2, and 4% solutions (1 drop of 50 muL) significantly decreased the IOP of normotensive rabbits in a dose-dependant manner. At the highest dose , the maximum reduction (5.6 +/- 0.65 mm Hg) was observed at 3 h. In a comp arative efficacy study, dipivalyl terbutalone was found to be more effectiv e than epinephrine. In the in vivo distribution after the topical administr ation of dipivalyl terbutalone, terbutaline was found only in the iris-cili ary body, whereas terbutalone was found in all parts of the eye studies. Th is work suggests the potential use of dipivalyl terbutalone as an antiglauc oma agent, representing a new chemical delivery system for terbutaline.