Dermal and underlying tissue pharmacokinetics of lidocaine after topical application.

The deep-tissue penetration of lidocaine below a dermally applied site was quantified in a rat model. The concentrations of lidocaine in tissues below the applied site were measured and compared with plasma concentrations and concentrations in similar tissues on the contralateral side. The direct penetration of lidocaine was predominant for the first 2 h up to a depth of about 1 cm below the applied site. A physiologically based pharmacokinetic model based on apparent tissue-tissue clearances and local blood flow to tissues is presented which adequately describes the concentration-time profiles of lidocaine in underlying tissues after dermal application. The apparent tissue-tissue clearances were estimated by nonlinear regression assuming first-order diffusional mass transfer of lidocaine between the various tissue compartments below the applied site in anesthetized rats. Tissue levels of lidocaine were estimated using simulations from the model with and without direct penetration and tissue blood supply. Dermal microcirculation is not a perfect sink for lidocaine.