Sponge delivery variables and tissue levels of 5-fluorouracil

Abstract

Aim: To study how the delivery of 5-fluorouracil (5-FU) to ocular tissues is affected by altering delivery variables.

Method: Sponge(s) soaked in radiolabelled 5-FU were placed between the conjunctiva and sclera of pig eyes. Application time, sponge size, sponge make (Altomed, Weck, Merocel), and 5-FU concentration were varied. Conjunctival and scleral tissue levels were determined in samples taken from the application site.

Results: Dose-response curves for scleral and conjunctival 5-FU levels against application time showed increasing tissue levels that reached a plateau after 2-3 minutes. Application beyond 3 minutes did not increase tissue levels. There was no difference in tissue levels between 7x4 and 3. 5x2 mm sponges. Altomed sponges produced 5-FU tissue levels that were twice as high as those obtained with Weck-cell (p<0.01) or Merocel (p<0.02) sponges. Changing the 5-FU concentration from 25 mg/ml to 6.25 mg/ml reduced the conjunctival concentration by a factor of 3.5 (p<0.003).

Conclusion: Application time up to 3 minutes, sponge make, and 5-FU concentration can have a large effect on the tissue delivery of 5-FU. Application time beyond 3 minutes, using 3.5x2 mm or 7x4 mm sponges, and replacing sponges every minute did not have a significant effect on tissue levels. This study models the effect that different variables can have on the ocular tissue levels of an antimetabolite applied intraoperatively.

Figure 1

Sites of conjunctival and scleral biopsies. Box shows site of sponge application.

Figure 2

Conjunctival tissue level of ¹⁴C 5-FU against duration of single application of Altomed sponge.

Figure 3

Scleral tissue level of ¹⁴C 5-FU against duration of single application of Altomed sponge.

Figure 4

Regional conjunctival tissue level of ¹⁴C 5-FU following single 5 minute application of either 7×4 mm or 3.5×2 mm Altomed sponge. Sites 1, 2, and 3 are shown in Figure 1.

Figure 5

Regional scleral tissue level of ¹⁴C 5-FU following single 5 minute application of either 7×4 mm or 3.5×2 mm Altomed sponge. Sites 1, 2, and 3 are shown in Figure 1.

Figure 6

Conjunctival tissue level of ¹⁴C 5-FU following either a single Altomed sponge applied for 5 minutes or an Altomed sponge replaced every minute for 5 minutes.

Figure 7

Scleral tissue level of ¹⁴C 5-FU following either a single Altomed sponge applied for 5 minutes or an Altomed sponge replaced every minute for 5 minutes

Figure 8

Conjunctival tissue level of ¹⁴C 5-FU following a single application using a Weck, Altomed, or Merocel sponge.

Figure 9

Conjunctival tissue level of ¹⁴C 5-FU following a single 5 minute application of an Altomed sponge soaked in either 25 mg/ml or 6.25 mg/ml ¹⁴C 5-FU solution.

Figure 10

Scleral tissue level of ¹⁴C 5-FU following a single 5 minute application of an Altomed sponge soaked in either 25 mg/ml or 6.25 mg/ml ¹⁴C 5-FU solution.