Effect of St John's wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females.
OBJECTIVE
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 x 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.
Wenk
Markus
M
Division of Clinical Pharmacology & Toxicology, Department of Internal Medicine, University Hospital, Basel, Switzerland. markus-aloisius.wenk@unibas.ch
Todesco
Liliane
L
Krähenbühl
Stephan
S
D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D020902:Hypericum; D008297:Male; D008875:Middle Aged; D014969:Xanthine Oxidase / Q000378:metabolism*
D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D014969:Xanthine Oxidase; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D006854:Hydrocortisone