Jpn. J. Pharmacol. 82 (2), 122-129 (2000)

Inhibitory Effect of Natural Furanocoumarins on Human Microsomal Cytochrome P450 3A Activity

Lian-Qing Guo1, Masahiko Taniguchi2, Yong-Qing Xiao2, Kimiye Baba2,
Tomihisa Ohta3 and Yasushi Yamazoe1,*

1Division╩of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences,
Tohoku University, Sendai 980-8578, Japan
2Division╩of Pharmacognosy, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1094, Japan
3Faculty╩of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
*╩To whom correspondence should be addressed.

Abstract: To investigate the possible drug interaction with herbal medicine, furanocoumarin derivatives isolated from several Umbelliferous crude drugs were examined for their inhibitory effects on a typical human drug metabolizing enzyme, cytochrome╩P450╩3A (CYP3A). Most furanocoumarins tested at 0.1╩mM reduced microsomal testosterone 6b-hydroxylation as an index of CYP3A activity to less than 50% of the control. In particular, the dimer and trimer derivatives of furanocoumarins showed striking inhibition, whose potencies were similar to that of a typical CYP3A inhibitor, ketoconazole. Preincubation of dimer types of furanocoumarins increased suppression but not most of the monomer derivatives, suggesting that the inhibition on CYP3A activity was caused by at least plural mechanisms. These results raised the possibility that the furanocoumarin containing herbal medicines may alter pharmacokinetics of co-ingested drugs similar to the case with grapefruit juice.

Keywords: Furanocoumarins, Herbal medicine, Human liver microsome, Cytochrome P450 3A, Inhibition

Copyrightę The Japanese Pharmacological Society 2000

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