Pharmacokinetic studies are essential to the process of developing new ocular drugs and drug delivery systems. Without knowledge of drug release, distribution and elimination, the new product cannot be used by humans. ODDL performs pharmacokinetic studies mainly with healthy rats and rabbits, both albinos and pigmented ones, using topical, subconjunctival, intracameral, intravitreal, subretinal and intravenous routes of drug administration. Quantitative and semi-quantitative concentrations of drugs or excipients in different parts of the eye are determined with non-invasive monitoring devices, such as in vivo fluorophotometry, fundus imaging and optical coherence tomography. The use of these devices significantly reduces the number of animals needed in the study, as the same animal can be monitored continuously. Invasive pharmacokinetics studies using tissue dissection and follow up analytics (liquid chromatography-mass spectrometry – LC/MS, liquid scintillation counting) can be performed. This is necessary when the test compound is not fluorescent. In the case of LC/MS analytics cassette-dosing is also possible, providing kinetic information on various compounds in the same experiment.
Pharmacodynamics studies are mainly performed with animal disease models, but in vitro cell models can be used for preliminary disease studies (e.g. neovascularization, oxidative stress). Endpoints in in vivo studies can be tailored based on the disease model. Typically, the methods are based on electroretinography (light responsive functions of the retina), visual evoked potential (functionality of optic nerve), fundus/ocular coherence topography/fluorescein angiography imaging (morphological status of retina and its vessels), measurement of intraocular pressure and immunohistochemistry of dissected tissues (biochemical mechanisms at cell level). Depending on the models and target disease, the pharmacodynamics can be investigated with mice, rats or rabbits.
If you need any further information, please contact our expert arto.urtti(at)uef.fi