Altered epidermal morphology secondary to lidocaine iontophoresis: in vivo and in vitro studies in porcine skin.

Iontophoresis is the process of delivering ionic drugs across the skin using electric current. Iontophoresis of lidocaine hydrochloride in 30 pigs in vivo and in 112 in vitro isolated perfused porcine skin flap (IPPSF) preparations produced a drug-specific alteration in the epidermis greater than or equal to 10 min after dosing. By light microscopy, this change was characterized by the appearance of flattened dark basophilic staining nuclei oriented parallel to the stratum corneum in the stratum granulosum and spinosum layers. In severe cases, this alteration extended into the deeper usually vacuolated stratum basale. The stratum corneum appeared normal. This unique morphological alteration showed an abrupt change from the stratum basale to stratum granulosum. An immune-mediated etiology can be ruled out since this alteration is observed both in vivo and in vitro. The severity of this change, graded on a scale of 0-3 (no change to severe), was best correlated to total transcutaneous lidocaine flux as estimated in IPPSF studies and to flux as estimated by current (mA-hr) in vivo. Electron microscopic changes following iontophoresis showed specific alterations in the tonofilaments of the epidermal cells. The tonofilaments appeared unrecognizable and resembled an amorphous matrix. In pigs followed through 10 days to study the resolution of this alteration, the epidermis reverted to normal within 6 days with no additional manifestations. In conclusion, lidocaine iontophoresis can induce in swine a unique dose-dependent non-immune-mediated epidermal alteration which is expected to have minimal toxicological significance.