Modelling Dermal Drug Distribution After Topical Application in Human

ABSTRACTPurposeTo model and interpret drug distribution in the dermis and underlying tissues after topical application which is relevant to the treatment of local conditions.MethodsWe created a new physiological pharmacokinetic model to describe the effect of blood flow, blood protein binding and dermal binding on the rate and depth of penetration of topical drugs into the underlying skin. We used this model to interpret literature in vivo human biopsy data on dermal drug concentration at various depths in the dermis after topical application of six substances. This interpretation was facilitated by our in vitro human dermal penetration studies in which dermal diffusion coefficient and binding were estimated.ResultsThe model shows that dermal diffusion alone cannot explain the in vivo data, and blood and/or lymphatic transport to deep tissues must be present for almost all of the drugs tested.ConclusionTopical drug delivery systems for deeper tissue delivery should recognise that blood/lymphatic transport may dominate over dermal diffusion for certain compounds.

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