A database (n = 50) consisting of values of solubility in water, SAQ, solubility in octanol, SOCT, molecular weight, MW, and maximum flux based on the delivery of total species containing a parent drug by its prodrugs through human skin in vitro from water has been integrated into the extended Flynn database (n = 114). In addition, data for two more recent contributions (n = 8) and one (n = 7) contribution that was overlooked for inclusion in the extended Flynn database were added to the prodrug database, as well as the data for the parent drugs (n = 6), to give n = 71 and n = 185 for the total integrated database. This integrated database was fit to five equations where the independent variable was SAQ, SOCT or MW alone or were combinations of SOCT and MW (Kasting–Smith–Cooper, KSC model) or SOCT, SAQ and MW (Roberts–Sloan, RS model). The RS equation gave the best fit: log JMAQ = −2.506 + 0.538 log SOCT + 0.462 log SAQ − 0.00402MW, r2 = 0.839, S.D. = 0.423 and the residual (Δlog JMAQ) was 0.474 log units. Integration of a substantial number of prodrugs into the extended Flynn database did not change the dependence of JMAQ on a balance of SAQ and SOCT. No trend in the effect of the prodrug being more or less water soluble than its parent drug on over- or underpredicting flux (±Δ′log JMAQ) by the RS model was found. Thus optimization of the SAQ of a prodrug in its design, as well as the design of new drugs, is indicated.