Evaluation of percutaneous permeation of flurbiprofen and ketoprofen after application of transdermal patches using a lateral sectioning approach in hairless rats.

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.

Comparison of peroxidase response to mental arithmetic stress in saliva of smokers and non-smokers.

Saliva is the first body fluid to encounter exogenous materials or gases such as cigarette smoke (CS). The aim of this study was to examine whether smoking affects oral peroxidase (OPO) reactivity to mental stress. The subjects were 39 non-smokers and 10 smokers. In the experiment, the Kraepelin psychodiagnostic test as a psychological stressor and saliva was sampled 30 min before, just before, immediately after, and 30 min after the beginning of the test. OPO reactivity to the test between smokers and non-smokers was measured in addition to uric acid concentration, flow rate, IgA, thiocyanate (SCN-) concentration, amylase activity as a salivary stress marker, and ultra-weak chemiluminescence (UCL) level, which is indicative of salivary antioxidative and antibacterial abilities. Moreover, we studied the effect of smoking on the response of salivary peroxidase (SPO) and myeloperoxidase (MPO) activity to mental stress, respectively. The results showed that the IgA concentration, amylase activity, SCN(- concentration, and UCL level are higher in the non-smoking group than smoking group and the IgA concentration and UCL level increased in the non-smokers significantly just after the Kraepelin test. The levels of SCN-) were higher in smokers than in non-smokers and OPO activity was greater in the non-smoking group in all sessions. Furthermore, only the non-smokers had significantly increased MPO activity just after the test. MPO may play a crucial role in the response to acute psychological stress besides inflammation, and CS suppresses this response significantly.