Influence of Garlic (Allium sativum) on the Pharmacokinetics of Docetaxel

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 P 450 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/m 2 ) 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/m 2 [95% confidence intervals (95% CI), 16.7-44.9]. Coadministration of garlic reduced mean clearance of docetaxel to 23.7 L/h/m 2 (95% CI, 15.5-31.8) and 20.0 L/h/m 2 (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.