Elimination of ketoprofen from the stratum corneum after topical administration with ketoprofen formulations in human subjects

Purpose: To assess the drug concentrations and elimination rate of ketoprofen in the stratum corneum following topical administration of two different formulations in human subjects for reference in the risk management of photocontact dermatitis caused by topical ketoprofen. Methods: Ketoprofen tape and gel were used as test formulations. The stratum corneum at the application sites was removed by tape-stripping at scheduled times after removal of the formulations. The ketoprofen concentration in the stratum corneum was determined by liquid chromatography with tandem mass spectrometry. Results: The ketoprofen concentration in the stratum corneum decreased and the elimination half-life in the stratum corneum was comparable between tape and gel after removal of the test formulations. The ketoprofen concentration in the stratum corneum decreased more rapidly after the subjects took a shower. Ketoprofen was not detected in the stratum corneum adjacent to the tape application sites. Conclusions: Ketoprofen in the stratum corneum appears to reach the lower limit of quantitation (0.005 μg) 12-16 days after removal of tape or gel. This period is similar to that recommended for avoiding ultraviolet light after removal of topical ketoprofen formulations in the Summary of Product Characteristics for topical ketoprofen in the European Union.