Prediction of skin absorption and local bioavailability from topical formulations remains a difficult task. An important challenge in forecasting topical bioavailability is the limited information available about local and systemic drug concentrations post-application of topical drug products. Commercially available transdermal patches, such as Scopoderm® (Novartis Consumer Health UK), offer an opportunity to test these experimental approaches as systemic pharmacokinetic data is available with which to validate a predictive model. The long-term research aim, therefore, is to develop a physiologically-based pharmacokinetic model (PBPK) to predict the dermal absorption and disposition of actives included in complex dermatological products. This work explored whether in vitro release and skin permeation tests (IVRT and IVPT, respectively), and in vitro and in vivo stratum corneum (SC) and viable tissue (VT) sampling data, can provide a satisfactory description of drug “input rate” into the skin and subsequently into the systemic circulation. In vitro release and skin permeation results for scopolamine were consistent with the previously reported performance of the commercial patch investigated. New skin sampling data on the dermatopharmacokinetics (DPK) of scopolamine also reflected accurately the rapid delivery of a “priming” dose from the patch adhesive, superimposed on a slower, rate-controlled input from the drug reservoir. The scopolamine concentration versus time profiles in SC and VT skin compartments, in vitro and in vivo, taken together with IVRT release and IVPT penetration kinetics, reflect the input rate and drug delivery specifications of the Scopoderm® transdermal patch and reveal the importance of skin binding with respect to local drug disposition. Further data analysis and skin PK modelling are indicated to further refine and develop the approach outlined.