Preclinical and Clinical Pharmacokinetics of a New Preservative-Free Bimatoprost 0.01% Ophthalmic Gel to Treat Glaucoma and Ocular Hypertension
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: Purpose: Pharmacokinetic evaluation of ocular penetration and systemic accumulation of preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel). Methods: In a preclinical study, pigmented rabbits received a single ocular administration of PFB 0.01% gel ( N = 15) or preserved bimatoprost 0.01% or 0.03% ophthalmic solution [PB 0.01% ( N = 15) or PB 0.03% ( N = 15)]. The aqueous humor, iris, and ciliary body were analyzed for bimatoprost+bimatoprost free acid. In a Phase 1, randomized, open-label clinical study, healthy participants received PFB 0.01% gel ( N = 20) or PB 0.01% ( N = 20) daily in each eye (Days 1–15). Bimatoprost levels in human plasma were analyzed on Days 1 and 15. All serological analyses used validated methods. Adverse events were collected throughout and ocular assessments were performed on Days 1 and 15. Results: In the preclinical study, Cmax (bimatoprost+bimatoprost free acid) for PFB 0.01% gel, PB 0.01%, and PB 0.03% was 50.2, 26.3, and 59.9 ng/mL; AUC 0.5–8 h was 134.0 ng·h/mL, 67.0 ng·h/mL, and 148.0 ng·h/mL. In the clinical study, systemic exposure to bimatoprost (AUC 0–last ) on Days 1 and 15 was lower for PFB 0.01% gel (0.5248 and 0.5645 ng·min/mL) than PB 0.01% (0.8461 and 0.7551 ng·min/mL), with no systemic accumulation of bimatoprost in either group. There were no clinically important differences between groups in ocular or systemic tolerability in the clinical study and no serious adverse events. Conclusions: PFB 0.01% gel showed improved ocular penetration compared with PB 0.01%. Systemic absorption was comparable, with a favorable clinical safety profile, supporting PFB 0.01% gel as a potential treatment for glaucoma and ocular hypertension.
Institutions: Aristotle University of Thessaloniki, AHEPA University Hospital, NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital, University College London, Thea (France), Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Universitair Ziekenhuis Leuven, KU Leuven
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4404136283