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  • Title: Intraocular pressure-lowering activity and in vivo disposition of dipivalyl terbutalone in rabbits.
    Author: Reddy IK, Vaithiyalingam SR, Khan MA, Bodor NS.
    Journal: Drug Dev Ind Pharm; 2001 Feb; 27(2):137-41. PubMed ID: 11266225.
    Abstract:
    The ocular hypotensive activity and in vivo disposition of dipivalyl terbutalone, a chemical delivery system for terbutaline, were investigated in the albino rabbit model. The dose-response relationship was assessed at drug concentrations ranging from 0.5 to 4% in normal saline. Intraocular pressure (IOP)-lowering activity of dipivalyl terbutalone was compared with epinephrine in equal concentrations. The in vivo disposition was investigated after topical administration of dipivalyl terbutalone at 4% dose level for which two metabolic products, terbutaline, and terbutalone, were monitored in different anterior segment tissues/fluid of albino rabbits, including corneal and iris-ciliary body homogenates and aqueous humor. The instillation of 0.5, 1, 2, and 4% solutions (1 drop of 50 microL) 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 comparative efficacy study, dipivalyl terbutalone was found to be more effective than epinephrine. In the in vivo distribution after the topical administration of dipivalyl terbutalone, terbutaline was found only in the iris-ciliary body, whereas terbutalone was found in all parts of the eye studied. This work suggests the potential use of dipivalyl terbutalone as an antiglaucoma agent, representing a new chemical delivery system for terbutaline.
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