Van Eyk A.D., Seifart H.I., Meyer D., Van Der Bijl P.
Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa; Department of Surgical Sciences, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
Van Eyk, A.D., Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa; Seifart, H.I., Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa; Meyer, D., Department of Surgical Sciences, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa; Van Der Bijl, P., Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa
PURPOSE: To compare the in vitro penetration of azithromycin and clarithromycin across both human and rabbit corneas. METHODS: In vitro diffusion studies were performed on frozen-thawed (liquid nitrogen, -80°C) corneas using a flow-through diffusion apparatus (24 hours, 20°C, 1.5 mL/h). Either phosphate-buffered saline (PBS) or 2 mg/g polyacrylic acid (Teargel) formulations of clarithromycin and azithromycin (1 or 4 mg/mL) were used in the donor chambers. Effluent samples collected (2 hours) were analyzed using binary high-performance liquid chromatography in conjunction with either UV/VIS or tandem mass spectrometry detection. RESULTS: The flux values of azithromycin (PBS and polyacrylic acid) across both types of corneas showed concentration dependence. Polyacrylic acid formulations showed a decrease in flux values of azithromycin across both types of corneas. For clarithromycin, flux values across both types of corneas were ~2.3-2.4 times higher than azithromycin. The flux values of azithromycin at 4 mg/mL (PBS and polyacrylic acid) across human cornea were higher than those across rabbit cornea, whereas the inverse was true at 1 mg/mL PBS for both drugs. CONCLUSIONS: Both macrolides penetrated the corneas, and the flux values were found to be concentration dependent (azithromycin). Clarithromycin had a higher diffusion rate across corneas than azithromycin. Although the human cornea had a higher permeability to azithromycin at a higher concentration, the inverse was found at lower concentrations for both drugs. Rabbit cornea can be used in general as an in vitro permeability model for human cornea; however, care must be taken with the extrapolation of results. © 2009 by Lippincott Williams & Wilkins.
azithromycin; carbomer; clarithromycin; phosphate buffered saline; polyacrylic acid; antimicrobial activity; article; concentration response; controlled study; drug concentration; drug penetration; high performance liquid chromatography; human; keratitis; liquid chromatography; nonhuman; priority journal; steady state; tandem mass spectrometry; Adult; Aged; Animals; Anti-Bacterial Agents; Azithromycin; Chromatography, High Pressure Liquid; Clarithromycin; Cornea; Corneal Ulcer; Diffusion; Eye Infections, Bacterial; Humans; Middle Aged; Permeability; Rabbits; Tandem Mass Spectrometry; Young Adult