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In vitro diffusion of the immunosuppressant tacrolimus through human and rabbit corneas.

PURPOSE
The aim of this study was to investigate the in vitro diffusion kinetics of tacrolimus (TAC) through rabbit and human corneas, and to evaluate the suitability of rabbit cornea as an in vitro permeability model for human cornea.


METHODS
A flow-through diffusion apparatus was used for all permeability experiments. The percentage of total (3)H-TAC diffusing across the corneas was determined over 24 h and fractions collected twice-hourly (20 degrees C; 1.5 mL/h). An F test was used for whole-curve comparisons, with a significance level of 5%.


RESULTS
Steady-state values for TAC across both types of corneas were not reached. Although the percentage of TAC diffusing across rabbit cornea was higher than that found for human cornea up to 18 h, there were no statistically significant differences. The percentages of total TAC diffusing across human and rabbit cornea at the 24-h time points were 0.38% +/- 0.02% and 0.36% +/- 0.01%, respectively.


CONCLUSIONS
Percentages of total TAC at the 24-h time points were approximately 4.9x and 4.1x higher than those found previously for cyclosporin A across human and rabbit corneas, respectively. Rabbit corneas are a suitable model for human corneas in in vitro permeability studies.