Dermal clearance model for epidermal bioavailability calculations.

A computational model for estimating dermal clearance in humans of arbitrary, nonmetabolized solutes is presented. The blood capillary component employs slit theory with contributions from both small (10 nm) and large (50 nm) slits. The lymphatic component is derived from previously reported clearance measurements of dermal and subcutaneous injections of (131)I-albumin in humans. Model parameters were fitted to both blood capillary permeability data and lymphatic clearance data. Small molecules are cleared largely by the blood and large molecules by the lymph. The combined model shows a crossover behavior at approximately 29 kDa, in acceptable agreement with the reported value of 16 kDa. When combined with existing models for stratum corneum permeability and appropriate measures of tissue binding, the developed model has the potential to significantly improve tissue concentration estimates for large or highly protein-bound permeants following dermal exposure.