Purchase this article with an account.
M. Diestelhorst, o. Doroshyenko, A. Lux, K. Abduljalil, A. Steinfeld, S. Dinslage, R. Sueverkruep, U. Fuhr; Comparative Ocular Pharmacokinetics of Fluorescein Following Application as Lyophilisate and Conventional Eye Drops. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5793.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
three randomized, cross-over studies were analyzed to evaluate the pharmacokinetics of fluorescein (F) administered as lyophilisate (L) or conventional eye drops 0.17% (D) to volunteers.
In 3 studies F was applied to 10, 12 and 22 volunteers as L to one eye and as D to the fellow eye, respectively. The dose was 68µg in studies 1 and 2; in study 3, a dose of 204µg F was applied as a single lyophilisate to one eye and as three eye drops (+1, 15, 30 min) to the fellow eye. In all studies, F concentrations in the cornea (C) and anterior chamber (AC) were measured by fluorophotometry (Fluorotron Master II, Ocumetrics, USA). Measurement times were: study 1: predose, every two minutes up to 30 min after dosing; study 2: predose, +15, 30, 45, 60, 120, 180 minutes. Study 3: predose, +15, 30, 45, 60, 120, 180, 240, 300, 360, 420 minutes. Pharmacokinetics of F obtained by non-compartmental methods (no correction for baseline fluorescence) were compared between formulations using bio-equivalence methods.
Inter-individual variability in F pharmacokinetics was high, with coefficients of variation (CVs) typically in the 100 % range. CVs were similar for L and D. Administration of L gave significantly higher concentrations than that of D. The Cmax in C and AC was 5.8-fold (90%CI 3.1-11.2) and 6.3-fold (90%CI 3.4-11.8) higher in study 1, 14,4-fold (90%CI 7.1-29.3) and 3.9-fold (90%CI 2.3-6.8) higher in study 2, and 8.3-fold (90%CI 4.5-15.3) and 5.3-fold (90%CI 3.5-7.9) higher in study 3, respectively. AUC0-t values of F in C and AC for L was increased 11.6-fold (90%CI 6.5-20.8) and 8.8-fold (90%CI 5.2-15.1) in study 1, 4.7-fold (90%CI 2.9-7.7) and 2.6-fold (90%CI 1.9-3.5) in study 2, and 4.5-fold (90%CI 2.8-7.2) and 3.7-fold (90%CI 2.7-5.1) in study 3, respectively. Absorption and elimination rates of F were not significantly affected by formulation.
Although none of the three studies covers the entire concentration vs. time profile with an appropriate sampling density, the data clearly show a significantly higher intraocular bioavailability of F when given as L compared to D. This is due to a slower loss of F for absorption from the L formulation. Depending on the physicochemical properties of a drug this may be essential for achieving effective drug concentrations in the eye for a sufficient period of time. This is one of the advantages of the new drug delivery system over conventional eye drops.
This PDF is available to Subscribers Only