Diffusion of metronidazole released from aqueous solution and a gel through human and rabbit corneas.
Metronidazole has been suggested as an adjunct in the treatment of Acanthamoeba keratitis. This study involves the permeation of metronidazole from topically applied solutions and gels through human and rabbit corneas. The permeation of metronidazole, from the solutions and gels through the corneas, was determined using a flow-through diffusion apparatus. Human (32) and rabbit (54) corneas were obtained from an eye bank and animal nursery farm, respectively. Experiments were conducted at 20 degrees C and over a time period of 24 hours. High-performance liquid chromatography (HPLC) analysis was used as a detection method. Statistical tests used included an Analysis of Variance (ANOVA) and Duncan's multiple range test, for a determination of the steady state, and a nonlinear regression analysis, using an F test, was used to compare entire curves. Flux rates for 0.5% and 1% metronidazole solutions across human corneas were found to be 14% and 30% higher, respectively, than for rabbit corneas. However, the flux rates of the 0.5% and 0.8% metronidazole gels across rabbit corneas were found to be 7% and 25% higher than those for human corneas. The flux rates measured for at least the first 10 hours were not, statistically, significantly different between the metronidazole released from aqueous solutions and from the gel. Steady-state flux rates of the 0.5% metronidazole aqueous and gel formulations were approximately half those of the 0.8% and 1% preparations. Because of the longer corneal contact times, it may be therapeutically advantageous to use 0.8% metronidazole concentrations in gels for treating Acanthamoeba keratitis infestations. Further in vivo studies on the ocular compatibility of these formulations need to be performed. The use of rabbit corneas as an in vitro permeability model for human corneas is supported by these studies.
van der Bijl
Pieter
P
Department of Pharmacology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa. pvdb@sun.ac.za
van Eyk
Armorél D
AD
Seifart
Heiner I
HI
Meyer
David
D
D000328:Adult; D000368:Aged; D000818:Animals; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D004058:Diffusion; D016503:Drug Delivery Systems; D005782:Gels; D006801:Humans; D008795:Metronidazole / Q000493:pharmacokinetics*; D008875:Middle Aged; D010539:Permeability; D011817:Rabbits; D012996:Solutions
D000981:Antiprotozoal Agents; D005782:Gels; D012996:Solutions; D008795:Metronidazole