Pharmacokinetic-pharmacodynamic model to predict drug concentrations and intraocular pressure lowering effect for a bimatoprost six-month slow-release system.

Introduction: Ophthalmic drug product development and dosing regimen selection depend on animal eye drug concentration-effect relationships since human eye tissues cannot be sampled for drug quantification. This study hypothesized that a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model developed based on dog studies can be applied to the human eye of different ages, based on physiological parameter adjustment, to predict drug concentrations and effects in response to a new 6-month slow-release, intracameral, intraocular pressure (IOP) lowering, anti-glaucoma bimatoprost implant.

Methods: Using previously reported dog concentration-effect relationship data at various doses, and the physiological parameters of dog eye, a PK-PD model was designed to predict dog aqueous humor drug concentrations and IOP lowering effects simultaneously for a given dose.