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Modelling ocular pharmacokinetics of fluorescein administered as lyophilisate or conventional eye drops

  • Pharmacokinetics and Disposition
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Abstract

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 (Cmax) and the areas under the concentration-time curve (AUC0-t ) values of fluorescein in the cornea and anterior chamber for lyophilisate were increased in the noncompartmental analysis: mean lyophilisate Cmax in the studies was 6.3- to 14.6-fold higher and mean AUC0–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.

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Acknowledgements

The authors are grateful to Olena Krasichkova and Stefan Mayer for the preparation of lyophilisates.

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Authors and Affiliations

  1. Department of Pharmacology, Clinical Pharmacology Unit, University of Cologne, Gleueler Str. 24, D-50931, Köln, Germany

    Khaled Abduljalil, Oxana Doroshyenko & Uwe Fuhr

  2. Department of Ophthalmology, University Hospital, University of Cologne, Köln, Germany

    Michael Diestelhorst, Anja Lux, Andre Steinfeld & Sven Dinslage

  3. Department of Pharmaceutical Technology, Pharmaceutical Faculty, University of Bonn, Bonn, Germany

    Richard Süverkrüp

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  1. Khaled Abduljalil
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Correspondence to Uwe Fuhr.

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Abduljalil, K., Diestelhorst, M., Doroshyenko, O. et al. Modelling ocular pharmacokinetics of fluorescein administered as lyophilisate or conventional eye drops. Eur J Clin Pharmacol 64, 521–529 (2008). https://doi.org/10.1007/s00228-007-0457-3

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  • DOI: https://doi.org/10.1007/s00228-007-0457-3

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