OBJECTIVES: The dispositions and pharmacokinetic parameters of non-steroidal anti-inflammatory drugs (NSAIDs) after patch applications have typically been evaluated on a whole-skin basis, and the detailed permeation profiles remain unclear. The aim of this study was to establish a new method for clearly analyzing the flow of drugs in the skin layers and evaluating the drug levels in the target area of the skin tissue. METHODS: The skin tissue areas where flurbiprofen and ketoprofen patches were applied were cut into 20 μm-thick lateral slices from the surface to the deepest layer and the drug concentrations in the slices were measured. RESULTS: The results revealed the presence of depth-dependent concentration gradients from the surface to the deep layer and that the drug concentration in the deepest layer was less than one tenth of the surface concentration for both flurbiprofen and ketoprofen. In addition, flurbiprofen yielded higher and more rapid concentrations in the deepest skin layer adjacent to the intramuscular tissue. CONCLUSIONS: The present data suggest that our technique involving lateral slicing of skin tissues and measurement of drug concentrations allows visual understanding of drug dispositions in the skin layers and makes it possible to evaluate the drug levels in the target area of the skin tissue.
OBJECTIVES: The dispositions and pharmacokinetic parameters of non-steroidal anti-inflammatory drugs (NSAIDs) after patch applications have typically been evaluated on a whole-skin basis, and the detailed permeation profiles remain unclear. The aim of this study was to establish a new method for clearly analyzing the flow of drugs in the skin layers and evaluating the drug levels in the target area of the skin tissue. METHODS: The skin tissue areas where flurbiprofen and ketoprofen patches were applied were cut into 20 μm-thick lateral slices from the surface to the deepest layer and the drug concentrations in the slices were measured. RESULTS: The results revealed the presence of depth-dependent concentration gradients from the surface to the deep layer and that the drug concentration in the deepest layer was less than one tenth of the surface concentration for both flurbiprofen and ketoprofen. In addition, flurbiprofen yielded higher and more rapid concentrations in the deepest skin layer adjacent to the intramuscular tissue. CONCLUSIONS: The present data suggest that our technique involving lateral slicing of skin tissues and measurement of drug concentrations allows visual understanding of drug dispositions in the skin layers and makes it possible to evaluate the drug levels in the target area of the skin tissue.