INHIBITION OF CHLORZOXAZONE METABOLISM, A CLINICAL PROBE FOR CYP2E1, BY A SINGLE INGESTION OF WATERCRESS

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