Cassette dosing pharmacokinetic studies for evaluation of ophthalmic drugs for posterior ocular diseases.
The purpose of this investigation was to evaluate the utility of cassette dosing as a means for increasing throughput and decreasing animal usage for intravitreal ocular pharmacokinetic studies. Pigmented rabbits received a single intravitreal injection of test article containing either a single compound or a mixture of up to five compounds. Samples of vitreous, choroid and retina were collected at predetermined intervals through 7 or 28 days after dosing. Concentrations of each compound were determined by LC/MS/MS, with subsequent pharmacokinetic data analysis. The ocular pharmacokinetic properties of four test compounds administered as a cassette were in agreement with the ocular pharmacokinetics of each compound when administered as a single entity. Cassette dosing was subsequently used to screen an additional 15 compounds, with injection of 5 compounds per study. Based on the results from these cassette-dosing studies, some compounds demonstrated favorable ocular pharmacokinetics, with sustained concentrations above 300 ng/g in retina for at least 1 week after dosing while other compounds showed either considerably less penetration into retina or a shorter residence time in the retina. These findings suggest that the cassette dosing approach can be used in evaluating the intravitreal ocular pharmacokinetic properties of compounds intended for ocular use.
Proksch
Joel W
JW
Global Preclinical Development, Bausch & Lomb, 1400 N. Goodman Street, Rochester, New York 14609, USA. Joel.W.Proksch@bausch.com
Ward
Keith W
KW
D000818:Animals; D002853:Chromatography, Liquid; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D011817:Rabbits; D012160:Retina / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D004364:Pharmaceutical Preparations