TY - JOUR
T1 - Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel
AU - Cox, Michael C.
AU - Low, Jennifer
AU - Lee, James
AU - Walshe, Janice
AU - Denduluri, Neelima
AU - Berman, Arlene
AU - Permenter, Matthew G.
AU - Petros, William P.
AU - Price, Douglas K.
AU - Figg, William D.
AU - Sparreboom, Alex
AU - Swain, Sandra M.
PY - 2006/8/1
Y1 - 2006/8/1
N2 - Purpose: The herbal supplement garlic (Allium sativum) is commonly used by cancer patients. Preclinical studies have shown that allicin, a major component of garlic, may affect cytochrome P450 3A4 (CYP3A4) activity. This study examines the influence of garlic supplementation on the pharmacokinetics of docetaxel, a CYP3A4 substrate. Experimental Design: Women with metastatic breast cancer were treated with docetaxel (30 mg/m2) given weekly for 3 of 4 weeks. Three days after the initial dose of docetaxel, patients received 600 mg of garlic twice daily for 12 consecutive days. Docetaxel pharmacokinetics were assessed during the first three administrations. Results: In 10 evaluable patients, the mean baseline clearance of docetaxel was 30.8 L/h/m2 [95% confidence intervals (95% CI), 16.7-44.9]. Coadministration of garlic reduced mean clearance of docetaxel to 23.7 L/h/m2 (95% CI, 15.5-31.8) and 20.0 L/h/m2 (95% CI, 13.3-26.7) on days 8 and 15, respectively (P = 0.17). Additional pharmacokinetic variables of docetaxel, including peak concentration (P = 0.79), area under the curve (P = 0.36), volume of distribution (P = 0.84), and half-life (P = 0.36), were also not statistically significantly different. The mean area under the curve ratio between day 15 and day 1 was 3.74 in three individuals with the CYP3A5* 1A/*1A genotype (all African American) compared with 1.02 in six individuals with the CYP3A5* 3C/*3C genotype (all Caucasian). Conclusions: This study indicates that garlic does not significantly affect the disposition of docetaxel. However, it cannot be excluded that garlic decreases the clearance of docetaxel in patients carrying a CYP3A5* 1A allele.
AB - Purpose: The herbal supplement garlic (Allium sativum) is commonly used by cancer patients. Preclinical studies have shown that allicin, a major component of garlic, may affect cytochrome P450 3A4 (CYP3A4) activity. This study examines the influence of garlic supplementation on the pharmacokinetics of docetaxel, a CYP3A4 substrate. Experimental Design: Women with metastatic breast cancer were treated with docetaxel (30 mg/m2) given weekly for 3 of 4 weeks. Three days after the initial dose of docetaxel, patients received 600 mg of garlic twice daily for 12 consecutive days. Docetaxel pharmacokinetics were assessed during the first three administrations. Results: In 10 evaluable patients, the mean baseline clearance of docetaxel was 30.8 L/h/m2 [95% confidence intervals (95% CI), 16.7-44.9]. Coadministration of garlic reduced mean clearance of docetaxel to 23.7 L/h/m2 (95% CI, 15.5-31.8) and 20.0 L/h/m2 (95% CI, 13.3-26.7) on days 8 and 15, respectively (P = 0.17). Additional pharmacokinetic variables of docetaxel, including peak concentration (P = 0.79), area under the curve (P = 0.36), volume of distribution (P = 0.84), and half-life (P = 0.36), were also not statistically significantly different. The mean area under the curve ratio between day 15 and day 1 was 3.74 in three individuals with the CYP3A5* 1A/*1A genotype (all African American) compared with 1.02 in six individuals with the CYP3A5* 3C/*3C genotype (all Caucasian). Conclusions: This study indicates that garlic does not significantly affect the disposition of docetaxel. However, it cannot be excluded that garlic decreases the clearance of docetaxel in patients carrying a CYP3A5* 1A allele.
UR - http://www.scopus.com/inward/record.url?scp=33748087822&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-06-0388
DO - 10.1158/1078-0432.CCR-06-0388
M3 - Article
C2 - 16899612
AN - SCOPUS:33748087822
SN - 1078-0432
VL - 12
SP - 4636
EP - 4640
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -