Sponge delivery variables and tissue levels of 5-fluorouracil.
OBJECTIVE
To study how the delivery of 5-fluorouracil (5-FU) to ocular tissues is affected by altering delivery variables.


METHODS
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).


CONCLUSIONS
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.
Wilkins
M R
MR
Wound Healing Research Unit, Department of Pathology, Institute of Ophthalmology, London.
Occleston
N L
NL
Kotecha
A
A
Waters
L
L
Khaw
P T
PT
D000287:Administration, Topical; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D003228:Conjunctiva / Q000737:chemistry / Q000378:metabolism*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012590:Sclera / Q000737:chemistry / Q000378:metabolism*; D015503:Surgical Sponges; D013552:Swine; D013997:Time Factors; D014018:Tissue Distribution
D000963:Antimetabolites; D002250:Carbon Radioisotopes; D005472:Fluorouracil