Stereoselective metabolism of OXY was evident following both transdermal and oral administration of OXY. The reduced pre-systemic metabolism of transdermally administered OXY compared to oral administration resulted in not only significantly lower DEO plasma concentrations, but also a different metabolite pattern. The differences between R-OXY and R-DEO following the two routes of administration support the potential for comparable clinical efficacy and reduced anticholinergic side-effects with transdermal treatment.

Background/aims: Surfactant mixtures are used in cosmetic and pharmaceutical formulas in order to establish product efficacy while maintaining mildness and skin lipids. The electron paramagnetic resonance (EPR) technique of the spin labeling method with a nitroxide spin probe is a valuable method in the study of biological membranes. The objective of this study was to define the influence of surfactant mixtures on intercellular lipid fluidity and correlate EPR spectral data with in vivo safety data. Methods: EPR experiment: EPR spectra of 5‐doxyl stearic acid (5‐DSA) labeled stratum corneum treated with sodium lauryl sulfate (SLS), sodium lauroyl glutamate (SLG) and their mixtures were measured and order parameters were calculated. Clinical testing: Fifteen healthy volunteers free of skin disease and with no history of atopic dermatitis were treated with SLS solutions (0.25%, 0.50%, 0.75%, 1.00%), 1.00% SLG solution and 1.00% surfactant mixture solutions: 0.75% SLS+0.25% SLG, 0.50% SLS+0.50% SLG, 0.25% SLS+0.75% SLG. One hundred μl of solution was applied using a polypropylene chamber for 24 h. Transepidermal water loss (TEWL) was measured with an evaporimeter before and after the application of surfactant solutions and each site was also visually graded according to Lee (1). Results: The order parameter (S) calculated from 1.00 %wt SLS treated stratum corneum was 0.56 ± 0.03, indicating disordering of lipid structure. On the contrary, the high S value (0.82 ± 0.02) for 1.00 %wt SLG suggests a reduced effect on the structured lipid, almost equaling the value of water. Treatment with 0.25 %wt, 0.50 %wt and 0.75 %wt SLS solutions revealed intermediate levels between 1.00 %wt SLG and SLS. The order parameters at each SLS concentration (0.25, 0.50, 0.75 and 1.00 %wt SLS) with 1.00 %wt SLG showed higher values than those of SLS only solutions. There were statistically significant differences between with and without 1.00 %wt SLG (P < 0.05). These results suggest that the addition of 1.00 %wt SLG inhibits the fluidization of intercellular lipid induced by SLS. The visual scores and TEWL values of 1.00% SLG solution were lower than those of the other test solutions (except for the vehicle control: deionized water). The 1.00% surfactant mixture solutions showed lower visual scores and TEWL values of the 1.00% SLS solution. An increase of SLG concentration decreased the visual scores and TEWL values. Order parameter S obtained from EPR spectra correlated with the clinical study. The correlation coefficient (r2) of visual score and TEWL values was 0.73 and 0.83, respectively. Conclusion: SLS disorder (fluidity) intercellular lipids at low concentrations, such as 0.25 %wt, presumably due to the SLS molecules being intercalated into the intercellular lipids. However, EPR spectral data suggest that the addition of 1.00 %wt SLG to an SLS solution (<1.00 %wt) inhibits the fluidization of intercellular lipid induced by SLS. A reasonable correlation between order parameters and human clinical data (visual scores and TEWL valu...

Sustained delivery over 4 days and multiple sites allow a convenient, well-tolerated, twice-weekly OXY TDS dosing. A low incidence of anticholinergic side effects is expected during clinical use because of the avoidance of presystemic metabolism and low DEO plasma concentrations. The consistent delivery, absorption, and pharmacokinetics should result in an effective treatment of patients with overactive bladder.

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Background: When skin is exposed to chemicals, raw materials interact with the lipid structure of the stratum corneum. At least two types of disorders can be distinguished – that of alkyl chains inside one lipid bilayer and that of lipid layer arrangement. Electron spin resonance (ESR) spectroscopy of a nitroxide spin label is a valuable method in the study of biological membranes. Objective: These experiments define the effect of anionic surfactants on the lipid bilayer of human stratum corneum. Methods: 5-Doxyl stearic acid (5-DSA) was used as the spin label. Sodium lauryl sulfate (SLS) and sodium lauroyl-L-glutamate (SLG) were the anionic surfactants studied. ESR spectrum measurements of surfactant-treated stratum corneum were performed and order parameters calculated. Results: 1 % of SLS leads to an obvious change in ESR spectra – from strongly to weakly immobilized spectra. The molecular motion of spin labels (5-DSA) in SLS-treated stratum corneum is different from that of spin labels in the untreated stratum corneum. The ESR spectra suggest that SLS affects the spin label binding to the lipid membrane and causes an increase in the mobility of bilayers. On the other hand, there were minimal changes in ESR spectra of 1% of SLG-treated stratum corneum. An increase in fluidity of skin lipid bilayers suggests a decrease in the skin barrier function. Conclusion: ESR may provide a facile and robust method to define the subclinical irritancy potential of anionic surfactants and other materials.