Quantitative vasoconstrictor assay for topical corticosteroids: the puzzling case of fluocinolone acetonide.

Abstract

The validity of the vasoconstrictor test has been questioned because of the apparent nonequivalence of some generic corticosteroid products. Our purpose was to determine the vasoconstrictor activity of a generic 0.025% fluocinolone acetonide ointment by two different methods, dilution by volume and dilution by area of application. Vasoconstrictor activity on a visual 4-point scale was measured in 20 volunteers. Topical fluocinolone acetonide ointment (0.025%) was tested by comparing dilution by volume (1:1, 1:3, and 1:7) in petrolatum and dilution by area of application. Fluocinolone release from the diluted ointments was also measured with an in vitro method. Dilution by area gave the expected results, a decreasing average vasoconstrictor score; but dilution by volume did not. Both the 1:1 and 1:3 dilutions inexplicably showed greater activity than the full-strength product; this finding was similarly reflected in the in vitro studies that showed a greater rate of drug release from the 1:1 and 1:3 dilutions. Dilution by area provides a useful quantitative assay for comparative vasoconstrictor activity.