Lian-Qing Guo1, Masahiko Taniguchi2, Yong-Qing
Xiao2, Kimiye Baba2,
Tomihisa Ohta3 and Yasushi Yamazoe1,*
1Divisionﾊof Drug Metabolism and Molecular Toxicology, Graduate
School of Pharmaceutical Sciences,
Tohoku University, Sendai 980-8578, Japan
2Divisionﾊof Pharmacognosy, Osaka University of Pharmaceutical
Sciences, Takatsuki 569-1094, Japan
3Facultyﾊof Pharmaceutical Sciences, Kanazawa University, Kanazawa
920-0934, Japan
*ﾊ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ﾊP450ﾊ3A (CYP3A). Most furanocoumarins
tested at 0.1ﾊ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