Safety and tolerability of pooled human immune globulins after topical ophthalmic administration in New Zealand White rabbits.

PURPOSE

To evaluate the safety and tolerability of pooled human immune globulins, Flebogamma 5% DIF and Flebogamma 10% DIF, administered by topical ophthalmic instillation to New Zealand White (NZW) rabbits.

METHODS

Male NZW rabbits were used in this study. In the acute single dose tolerability study, rabbits (n = 12) received a single topical dose of Flebogamma 5% DIF. In the two-week repeated-dose tolerability study, rabbits (n = 5 for each group) were administered either Flebogamma 5% DIF or Flebogamma 10% DIF by topical bilateral administration four times daily (q.i.d.) between 8 am and 6 pm for a period of two weeks. Full ophthalmic examinations were conducted to evaluate ocular tolerability at baseline, Day 7, and Day 14.

RESULTS

In the acute single dose study, mild hyperaemia was observed in 1 out of 4 eyes at each 4 h and 24 h post-instillation of Flebogamma 5% DIF. In the repeated dose study, no ocular signs were detected after q.i.d. topical instillation of Flebogamma 5% DIF, while Flebogamma 10% DIF resulted in mild hyperaemia in 8 out of 10 eyes on Day 7, and 5 out of 10 eyes on Day 14. No positive corneal fluorescein staining was detected. Schirmer tear test results were unremarkable. No other ocular signs were observed. Administration of immune globulins had no effect on intraocular pressure.

CONCLUSIONS

Flebogamma 5% DIF and Flebogamma 10% DIF were well-tolerated by NZW rabbits following single and repeat dose topical ophthalmic administration, supporting the future development of topical pooled human immune globulins for the treatment of ocular surface disease.