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Effect of St John's wort on the activities of CYP1A2, CYP3A4, CYP2D6, N‐acetyltransferase 2, and xanthine oxidase in healthy males and females
Author(s) -
Wenk Markus,
Todesco Liliane,
Krähenbühl Stephan
Publication year - 2004
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2003.02049.x
Subject(s) - cyp1a2 , dextromethorphan , cyp2d6 , cyp3a4 , urine , xanthine oxidase , zolpidem , endocrinology , chemistry , medicine , pharmacology , cytochrome p450 , metabolism , biochemistry , enzyme , insomnia
Aims To investigate the influence of St. John's wort (SJW) on CYP3A4, CYP1A2, CYP2D6, N‐acetyltransferase 2 (NAT2), and xanthine oxidase (XO) activities in healthy males and females. Methods Eight males and eight females were treated with SJW extract (3 × 300 mg day −1 ) for 14 days. Assessment of CYP1A2, NAT2, XO, CYP2D6, and CYP3A4 activities was performed before and at the end of the study period, using caffeine, dextromethorphan, and endogenous cortisol as probes. The corresponding metabolic ratios measured were 17MX/137MX in saliva and (AFMU+1MX+1MU)/17MU in urine for CYP1A2, AFMU/1MX for NAT2, 1MU/1MX for XO, DOR/DMO for CYP2D6, 3MM/DMO and 6OHC/C for CYP3A4, all determined in urine. Results The ratios of the treatment to baseline values for CYP3A4 using cortisol as the probe were 1.5 [95% confidence interval (CI) 1.3, 1.9] for males, and 1.9 (1.1, 3.0) for females. The corresponding ratios using dextromethorphan as the probe for CYP2D6 were 0.9 (95% CI 0.5, 2.1) for males and 1.9 (1.3, 3.2) for females. For CYP1A2, a significant increase in the metabolic ratios was found only for females (ratio of values 1.2; 95% CI 1.1, 1.4). No influence of SJW on CYP2D6, NAT2, and XO activities was observed. Conclusions An induction of CYP3A4 by SJW was confirmed. CYP1A2 appears to be induced by SJW only in females. The activities of CYP2D6, NAT2, and XO were not affected by SJW.