Effect of Trigonella foenum-graecum L. on Metabolic Activity of CYP2D6 and CYP3A4.
BACKGROUND
The present study investigated the effect of fenugreek seeds powder and its alcoholic extract on metabolic activity of drug-metabolizing enzymes CYP2D6 and CYP3A4.


METHODS
Dextromethorphan (DEX) was used as a probe for measuring metabolic activity, based on its CYP2D6- and CYP3A4-mediated metabolism to dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively. For the in vitro investigations, DEX (25µM) was incubated with human liver microsomes and NADPH and tested with and without the fenugreek extract. For the in vivo study, phase I, 6 subjects received a single dose of DEX (30 mg); in phase II, after washout period, the fenugreek seeds powder was administered for 1 week and DEX was administered with its last dose.


RESULTS
In vitro, fenugreek extract inhibits CYP2D6-mediated O-demethylation of DEX. Higher concentrations (50 and 100µg/ml) of extract inhibit CYP2D6 and CYP3A4 activity. In vivo results indicated that fenugreek does not significantly inhibit CYP2D6 and CYP3A4 metabolic activity. There was no significant change in the levels of DEX metabolites (DOR 12% and 3-MM 9%) excreted in urine and their urine metabolic ratios (P values: 0.257 and 0.333 DEX/DOR and DEX/3-MM, respectively).


CONCLUSIONS
In vitro and in vivo observations suggested that fenugreek may not have substantial effect on the metabolic activity of CYP2D6 and CYP3A4.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Fahad I
FI
Al-Jenoobi
Areej A
AA
Al-Thukair
Mohd Aftab
MA
Alam
Fawkeya A
FA
Abbas
Abdullah M
AM
Al-Mohizea
Khalid M
KM
Alkharfy
Saleh A
SA
Al-Suwayeh
D000328:Adult; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003915:Dextromethorphan / Q000032:analysis / Q000378:metabolism / Q000652:urine; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010936:Plant Extracts / Q000494:pharmacology*; D029910:Trigonella / Q000737:chemistry*; D055815:Young Adult
D010936:Plant Extracts; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A