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Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress
Author(s) -
Leclercq Isabelle,
Desager JeanPierre,
Horsmans Yves
Publication year - 1998
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(98)90147-3
Subject(s) - chlorzoxazone , ingestion , pharmacokinetics , pharmacology , watercress , chemistry , isoniazid , cyp2e1 , metabolism , medicine , biochemistry , food science , cytochrome p450 , pathology , tuberculosis
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 isoniazid 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. Clinical Pharmacology & Therapeutics (1998) 64 , 144–149; doi: