Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel

Michael C. Cox, Jennifer Low, James Lee, Janice Walshe, Neelima Denduluri, Arlene Berman, Matthew G. Permenter, William P. Petros, Douglas K. Price, William D. Figg, Alex Sparreboom, Sandra M. Swain*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4636-4640
Number of pages5
JournalClinical Cancer Research
Volume12
Issue number15
DOIs
StatePublished - 1 Aug 2006
Externally publishedYes

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