Blood or plasma to skin distribution of drugs: A linear free energy analysis

Data on distribution coefficients from blood or plasma to rat skin and rabbit skin have been compiled. From previous work on blood/plasma to brain or to muscle it is apparent that distributions from blood and plasma can be combined, and we show that it is possible to combine data on distribution to rat skin and rabbit skin. The combined set of blood/plasma distribution to rat and rabbit skin for 59 compounds, as log Pskin, can be correlated through a linear free energy equation with a correlation coefficient of 0.856 and a standard deviation of 0.26 log units. The predictive capability of the equation has been assessed through training and test sets, and it is shown that the S.D. value of 0.26 log units is a good estimate of the predictive ability. The equation for log Pskin has been compared to equations for a large number of possible model processes, using two mathematical methods. It is shown that there is no process amongst those we have examined that has any advantage over the present in silico linear free energy equation for the estimation of further values of log Pskin.