title: In vitro diffusion of mitomycin-C into human sclera after episcleral application: impact of diffusion time.
abstract: The purpose of this study was to investigate the impact of different diffusion times of mitomycin-C (MMC) on the intrascleral concentration vs depth profile of MMC in an experimental model. Scleral quadrants of eight human donor eyes were exposed to sponges soaked with MMC for an application time of 1 min. After irrigation with 40 ml saline, we allowed further diffusion of MMC in the sclera for 1, 5, 14 and 29 min until the specimens were further processed. A central 8 mm diameter scleral disk was horizontally dissected with a kryotome at -20 degrees C. MMC concentrations of six layers of 140 microm thickness were analysed by means of high-performance liquid chromatography. The MMC concentrations (microg g(-1)) of layer 1 were: 13.45+/- 5.9 (mean +/- S.D. at 2 min diffusion time), 7.6+/-2.5 (6 min diffusion), 5.6+/-3.1 (15 min diffusion) and 3.6+/-1.7 (30 min diffusion). The corresponding MMC concentrations of layer 6 were: 0.61+/-0.48, 1.47 +/-0.66, 1.83+/-0.42 and 2.98+/-0.97 microg g(-1). The superficial concentration of intrascleral MMC decreased with increasing diffusion time, the deep concentrations increased. After 30 min of diffusion time, equal concentrations of MMC were found in all layers. Even with current low-dose application regimens of MMC the concentrations in the inner side of the sclera rapidly increase beyond the limits of the therapeutic range. Owing to this fast diffusion of MMC, the only means of reducing ciliary body concentrations of MMC is to reduce the dose.
authors.affiliation: Department of Ophthalmology, University of Vienna, Austria. michael.georgopoulos@akh-wien.ac.at
authors.forename: M
authors.initials: M
authors.lastname: Georgopoulos
authors.forename: C
authors.initials: C
authors.lastname: Vass
authors.forename: I
authors.initials: I
authors.lastname: El Menyawi
authors.forename: S
authors.initials: S
authors.lastname: Radda
authors.forename: W
authors.initials: W
authors.lastname: Graninger
authors.forename: R
authors.initials: R
authors.lastname: Menapace
mesh_terms: D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D006801:Humans; D007552:Isotonic Solutions; D016685:Mitomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D012590:Sclera / Q000378:metabolism*; D012965:Sodium Chloride / Q000008:administration & dosage; D007507:Therapeutic Irrigation; D013997:Time Factors; D014130:Trabeculectomy / Q000379:methods
chemical_list: D007552:Isotonic Solutions; D019384:Nucleic Acid Synthesis Inhibitors; D012965:Sodium Chloride; D016685:Mitomycin