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

Authors' Affiliations: ¹ Clinical Pharmacology Research Core; ² Breast Cancer Section, Medical Oncology Branch, Center for Cancer Research; ³ Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis; and ⁴ Molecular Pharmacology Section, National Cancer Institute, Bethesda, Maryland; and ⁵ West Virginia University Health Sciences Center, Morgantown, West Virginia

Requests for reprints: Sandra M. Swain, Breast Cancer Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Room 5101, Building 8, 8901 Wisconsin Avenue, Bethesda, MD 20889. Phone: 301-451-6882; E-mail: swains{at}mail.nih.gov.

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.

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