Hairless mouse skin permeability coefficients measurements

Table A1 Hairless Mouse Skin Permeability Coefficient Measurements... 

Figure 15.1 through Figure 15.6 show skin permeability coefficient measurements from hairless mouse, hairless rat, rat, shed snake, and the lesser-studied animals (guinea pig, marmoset, rabbit, pig, dog, mouse, nude rat) plotted as a function of log In Figure 15.1 to Figure 15.4 and Figure 15.6, compounds that were more than 90% ionized are identified by the form of the dominant ionic species (that is, cation, anion, or zwitterion) and labeled as excluded. Ionized species with undetermined log are plotted to the left of the dashed vertical line located at log = -6.0. Cations are plotted at log = -6.5, anions at log = -7.0, and zwitterions at log = -7.5. A few permeability coefficient measurements that are... 

Table A1 lists and Figure 15.1 shows 144 permeability coefficient values for 83 eompounds (83 fully validated and 61 excluded data points 45 fully validated compounds) measured in hairless mouse skin. All of the measurements excluded from this database were more than 90% ionized. Etorphine is distinguished on this figure because Vecchia and Bunge (2002b) used the fact that the human permeability coefficient is larger than the hairless mouse permeability coefficient to support exclusion of the measurement from the fully validated database for human skin. Notice that the hairless mouse permeability coefficient of etorphine is consistent with measurements for other cations, which was not the case with the human permeability coefficient for etorphine (Vecchia and Bimge, 2002b).

Behl et al. studied the effect of prolonged contact of hairless mouse skin with water on permeability coefficients. The authors showed that permeability coefficients increase after extended periods of hydration. Because other permeability coefficients in the database we have assembled were measured on previously unhydrated skins or skins that were hydrated for short periods, the permeability coefficients with the shortest hydration time (0.3 to 0.8 h) from Table 1 were selected for the validated database. Permeability coefficients were determined with either water or ethanol as a copenetrant. The concentrations were dilute (alcohol concentrations less than 10 M) and probably were not damaging. Six reported measurements were averaged for methanol, two for ethanol, and two for butanol, and permeability coefficients were reported singly for hexanol, heptanol, and octanol. Although this article did not specify the diffusion cell temperature, subsequent articles by the same authors describing similar data indicated that the temperature was 37°C (e.g., Behl and Barrett, 1981 Behl, El-Sayed, et al., 1983 Behl, Linn, et al., 1983). It seems hkely that the temperature was also 37°C in the experiments described in this article. 

The permeability coefficient of etorphine was taken from Table I. Three measurements on hairless mouse skin were averaged. 

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