In Vivo Pharmacokinetics of Injectable, Intravitreal, Sustained-Release Latanoprost Formulations

Abstract

Purpose: To study the in vivo pharmacokinetics of injectable, intravitreal, sustained-release latanoprost formulations

Methods: In vivo anterior chamber drug levels were measured in New Zealand White rabbits receiving single doses of one of two formulations of sustained-release latanoprost administered by intravitreal injection. Aqueous humor samples were obtained weekly and analyzed for latanoprost acid concentrations using high-performance liquid chromatography with mass spectrometry.

Results: Sustained levels of latanoprost acid in the aqueous humor were demonstrated for 3 to 7 months in animals injected with single doses of sustained-release latanoprost formulations. The sustained-release formulation containing 559 µg of latanoprost demonstrated sustained levels of anterior chamber latanoprost acid which decreased to an average latanoprost acid aqueous humor level of 17.5 pg/mL on day 84. The sustained-release formulation containing 1118 µg of latanoprost demonstrated sustained anterior chamber levels of latanoprost acid which decreased to an average latanoprost acid aqueous humor level of 19.1 pg/mL on day 231.

Conclusions: In vivo anterior chamber levels of latanoprost acid were sustained for up to 7 months and were well-tolerated in rabbits receiving sustained-release latanoprost formulations injected intravitreally.

Keywords: 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • 445 cataract • 557 inflammation