Drug Interactions with Normal and TEN Epidermal Keratinocytes

Philippe      Paquet; Philippe      Delvenne; Gerald      E. Pierard

Abstract

Human epidermal keratinocytes (EKs) are metabolically involved in various drug transport mechanisms, as well as in detoxification or activation processes. The overall cell mechanisms of drug metabolization, and more specifically drug processing are reviewed in normal EKs. The overall drug metabolism involves different phases corresponding to the uptake, biotransformation and anti-transport steps. In EKs, both the enzymes and transportassociated proteins are different from those involved in the hepatocyte metabolism. Some cytochrome P450 enzymes and the flavin-containing mono-oxygenases are particularly involved in EKs. Basically, EKs represent key cells likely involved during the initial stage of drug-induced toxic epidermal necrolysis (TEN). Only limited advances have been made so far in this field. Nevertheless, mitigating EKs metabolic disturbances in TEN probably represent a promising specific treatment of the disease.

Keywords: Drug metabolism, toxic epidermal necrolysis, drug disposition, biotransformation, anti-transport mechanism, cytochrome P450, keratinocyte, aromatic anti-epileptics, lamotrigine, pantoprazole