Simulation of Tobramycin Pharmacokinetics After Topical Ophthalmic Administration

Conference: CRS
Software: GastroPlus®
Division: Simulations Plus


Introduction: Tobramycin belongs to the class of aminoglycoside antibiotics. It does not bind to serum proteins [1], is eliminated mainly by renal secretion [2] and is poorly absorbed from the gastrointestinal tract [3]. Traditionally, intravenous (i.v.) administration is used to treat bacterial infections. Topical ophthalmic suspension is frequently used  to treat ocular conditions with risk of bacterial ocular infections [4]. The current work describes simulations of tobramycin ocular PK after topical administration in rabbit and human using a new ocular drug delivery module, which has been developed as a part of the Additional Dosage Routes Module in GastroPlus™ (Simulations Plus, Inc.).

Methods: The new ocular model describes the eye as a collection of 8 compartments, including a pre-corneal area (tear film and the conjunctival sac), cornea, conjunctiva, aqueous humor, iris-ciliary body/lens, vitreous humor, retina and choroid/sclera. The passive diffusion of drug between different compartments is dependent on physiological (e.g. surface area) and drug-dependent physicochemical properties (e.g. permeability) for each compartment. Mechanisms such as nasolacrimal drainage, ocular metabolism, melanin binding, etc., have also been incorporated into this model. The ocular model is connected to the systemic pharmacokinetic model in GastroPlus to simulate drug appearance in plasma after ocular administration, as well as drug uptake by eye tissues from plasma after oral or systemic administration

38th Controlled Release Society (CRS) Annual Meeting and Exposition, July 30 – August 3, 2011, National Harbor, MD

By Viera Lukacova, Siladitya Ray Chaudhuri, Michael Bolger, Walter Woltosz