Objective  

The objective of this evaluation was to model ocular pharmacokinetics of fluorescein administered as conventional eye drops and as lyophilisate to healthy volunteers in order to assess the relative bioavailability of the lyophilisate formulation.

Methods  

A total of 44 healthy subjects received equivalent doses of fluorescein as lyophilisate to one eye and as eye drops to the fellow eye in three individual studies. Fluorescein concentrations in the cornea and anterior chamber were measured by fluorophotometry. Data were analyzed by noncompartmental methods (WinNonlin software) and by compartmental population pharmacokinetic methods (NONMEM software).

Results  

Compared to eye drops, both maximum fluorescein concentrations (C_max) and the areas under the concentration-time curve (AUC_0-t ) values of fluorescein in the cornea and anterior chamber for lyophilisate were increased in the noncompartmental analysis: mean lyophilisate C_max in the studies was 6.3- to 14.6-fold higher and mean AUC_0–t was 4.7- to 8.9-fold higher for ocular concentrations in the three studies. A three-compartment open model with first-order elimination from the anterior chamber adequately described population data. Estimated fluorescein systemic bioavailability (F) via the ocular route from lyophilisate relative to eye drops was 3.7-fold higher (95% CI 2.6–4.8).

Conclusion  

The data clearly show a considerably superior intraocular bioavailability of fluorescein when given as lyophilisate compared to conventional eye drops. There is a clear pharmacokinetic advantage of the lyophilisate preparation.