Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress

Leclercq, Isabelle [UCL] Horsmans, Yves [UCL] Desager, Jean-Pierre [UCL]

To investigate the effect of watercress on the metabolism of chlorzoxazone, an in vivo probe for CYP2E1, the oral pharmacokinetics of chlorzoxazone was studied in 10 healthy volunteers before and after a single ingestion of a watercress homogenate (50 gm). A third chlorzoxazone pharmacokinetic study was performed after a 1-week treatment with isoniazid (300 mg/day), a well-known CYP2E1 inhibitor. Ingestion of watercress or isoniazid did not affect the oral absorption of chlorzoxazone. The area under the chlorzoxazone plasma concentration-time curve was significantly increased by 56% (p < 0.05) after watercress ingestion and by 135% (p < 0.001) with isoniaxid treatment. Similarly, chlorzoxazone elimination half-life was prolonged after watercress (53%; p < 0.05) and isoniazid (104%; p < 0.01) administration. These results show that a single ingestion of watercress inhibits the hydroxylation of chlorzoxazone, an in vivo probe for CYP2E1.