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The Influence of St. John's Wort on CYP2C19 Activity with Respect to Genotype

From the Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China (Dr. L.-S. Wang, Dr. Zhu, Dr. El-Aty, Dr. G. Zhou, Dr. Z. Li, Dr. Chen, Dr. Liu, Dr. Tang, Dr. An, Dr. Q. Li, Mr. D. Wang, Dr. H.-H. Zhou) and Department of Cardiovasology, First Affiliated Hospital, Guangzhou Medical College, Guangzhou, China (Dr. Wu).

Induction of cytochrome P450 isozymes is the major cause for clinical drug interactions of St. John's wort. The relationships of St. John's wort to cytochrome P450 isoforms have been fully investigated, but its effect on CYP2C19 is lacking. Thus, the aim of the present study was to observe the effect of St. John's wort on CYP2C19 activity using CYP1A2 as a control. Twelve healthy adult men—6 extensive metabolizers of CYP2C19 (2C19^*1/2C19^*1) and 6 poor metabolizers (4 2C19^*2/2C19^*2 and 2 2C19^*2/2C19^*3)—were enrolled in a two-phase, randomized, crossover manner. All subjects took a 300-mg St. John's wort tablet or placebo three times daily for 14 days, and then the activities of CYP2C19 and CYP1A2 were measured using mephenytoin and caffeine. It was found that St. John's wort treatment significantly increased CYP2C19 activity in CYP2C19 wild-genotype subjects, with urinary 4'-hydroxymephenytoin excretion raised by 151.5% ± 91.9% (p = 0.0156), whereas no significant alteration was observed for CYP2C19 poor metabolizers. Repeated St. John's wort administration did not affect the CYP1A2 phenotypic ratio for both CYP2C19 genotype subjects. In conclusion, St. John's wort is an inducer to the human CYP2C19, and clinicians should pay great attention when St. John's wort is added to or withdrawn from an existing drug regimen containing substrates for such enzymes.

Key Words: St. John's wort • rifampicin • CYP2C19 • drug interactions • poor metabolizers • extensive metabolizers

Address for reprints: Professor Hong-Hao Zhou, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, China.

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