[12] Chlorzoxazone: An in vitro and in vivo substrate probe for liver CYP2E1

Cytochrome P4502E1 (CYP2E1) is involved in the oxidation of ethanol and a diverse group of suspect carcinogens, including nitrosamines, benzene, phenol, chloroform, trichloroethylene, ethylene dihalides, methylene dihalides, styrene, butadiene, vinyl halides, and urethane. The same chemical probe would have had to be convenient for in vitro studies, including the determination of CYP2E1 catalytic activities in microsomal preparations or in cell cultures. Chlorzoxazone, a potent muscle relaxant used in the treatment of painful muscle spasms, has been shown to be an ideal chemical probe specific for CYP2E1 in both in vitro and in vivo studies. In vitro studies comparing the abilities of several purified recombinant human P450 enzymes have demonstrated that CYP2E1 is the major catalyst of chlorzoxazone 6-hydroxylation in human liver. Data obtained from in vivo studies in alcoholic patients, before or after ethanol withdrawal, or in patients treated with either CYP2E1 inducers (isoniazid) or inhibitors (disulfiram) are in agreement with data obtained from in vitro liver microsomal preparations. Therefore, chlorzoxazone should be a suitable in vitro and in vivo probe for human liver CYP2E1.