Effects of garlic (Allium sativum L.) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers.
Garlic (Allium sativum L.) is a commonly used food and herbal supplement. The objective of this study was to assess in healthy volunteers (N = 14) the influence of a garlic extract on the activity of cytochrome P450 (CYP) 2D6 and 3A4. Probe substrates dextromethorphan (CYP2D6) and alprazolam (CYP3A4) were administered orally at baseline and again after treatment with garlic extract (3 x 600 mg twice daily) for 14 days. Urinary dextromethorphan/dextrorphan ratios and alprazolam plasma concentrations were determined by HPLC at baseline and after garlic extract treatment. The ratio of dextromethorphan to its metabolite was 0.044 +/- 0.48 at baseline and 0.052 +/- 0.095 after garlic supplementation. There were no significant differences between the baseline and garlic phases (P > or =.05). For alprazolam, there were no significant differences in pharmacokinetic parameters at baseline and after garlic extract treatment (all P values > or =.05; maximum concentration in plasma, 27.3 +/- 2.6 ng/mL versus 27.3 +/- 4.8 ng/mL; time to reach maximum concentration in plasma, 1.9 +/- 1.4 h versus 2.4 +/- 1.8 h; area under the time-versus-concentration curve, 537 +/- 94 h. ng. mL(-1) versus 548 +/- 159 h. ng. mL(-1); half-life of elimination, 13.7 +/- 4.4 h versus 14.5 +/- 4.3 h). Our results indicate that garlic extracts are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathway of metabolism.
Markowitz
John S
JS
Laboratory of Drug Disposition and Pharmacogenetics, Medical University of South Carolina, Charleston, SC 29425, USA.
Devane
C Lindsay
CL
Chavin
Kenneth D
KD
Taylor
Robin M
RM
Ruan
Ying
Y
Donovan
Jennifer L
JL
D000328:Adult; D000525:Alprazolam / Q000493:pharmacokinetics; D019540:Area Under Curve; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003915:Dextromethorphan / Q000493:pharmacokinetics; D019587:Dietary Supplements; D004220:Disulfides; D005260:Female; D005737:Garlic; D006207:Half-Life; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D013441:Sulfinic Acids / Q000378:metabolism
D004220:Disulfides; D007527:Isoenzymes; D013441:Sulfinic Acids; C006452:allicin; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000525:Alprazolam