BACKGROUND AND OBJECTIVE: St John's wort (SJW), a herbal antidepressant, is commonly used by cancer patients, and its component hyperforin is a known inducer of the cytochrome P450 (CYP) isoenzyme 3A4. Here, the potential pharmacokinetic interaction between SJW and the sensitive CYP3A4 substrate docetaxel was investigated. METHODS: In ten evaluable cancer patients, the pharmacokinetics of docetaxel (135 mg administered intravenously over 60 min) were compared before and after 14 days of supplementation with SJW (300 mg extract [Hyperiplant(®)] three times daily). RESULTS: SJW supplementation resulted in a statistically significant decrease in the mean area under the docetaxel plasma concentration-time curve extrapolated to infinity (AUC∞) from 3,035 ± 756 to 2,682 ± 717 ng · h/mL (P = 0.045). Furthermore, docetaxel clearance significantly increased from 47.2 to 53.7 L/h (P = 0.045) after SJW intake. The maximum plasma concentration and elimination half-life of docetaxel were (non-significantly) decreased after SJW supplementation. In addition, the incidence of docetaxel-related toxicities was lower after SJW supplementation. CONCLUSION: These results suggest that concomitant use of docetaxel and the applied SJW product should be avoided to prevent potential undertreatment of cancer patients.
BACKGROUND AND OBJECTIVE: St John's wort (SJW), a herbal antidepressant, is commonly used by cancer patients, and its component hyperforin is a known inducer of the cytochrome P450 (CYP) isoenzyme 3A4. Here, the potential pharmacokinetic interaction between SJW and the sensitive CYP3A4 substrate docetaxel was investigated. METHODS: In ten evaluable cancer patients, the pharmacokinetics of docetaxel (135 mg administered intravenously over 60 min) were compared before and after 14 days of supplementation with SJW (300 mg extract [Hyperiplant(®)] three times daily). RESULTS: SJW supplementation resulted in a statistically significant decrease in the mean area under the docetaxel plasma concentration-time curve extrapolated to infinity (AUC∞) from 3,035 ± 756 to 2,682 ± 717 ng · h/mL (P = 0.045). Furthermore, docetaxel clearance significantly increased from 47.2 to 53.7 L/h (P = 0.045) after SJW intake. The maximum plasma concentration and elimination half-life of docetaxel were (non-significantly) decreased after SJW supplementation. In addition, the incidence of docetaxel-related toxicities was lower after SJW supplementation. CONCLUSION: These results suggest that concomitant use of docetaxel and the applied SJW product should be avoided to prevent potential undertreatment of cancer patients.
Authors: Bernard J Komoroski; Robert A Parise; Merrill J Egorin; Stephen C Strom; Raman Venkataramanan Journal: Clin Cancer Res Date: 2005-10-01 Impact factor: 12.531
Authors: Martina Hennessy; D Kelleher; J P Spiers; M Barry; P Kavanagh; D Back; F Mulcahy; J Feely Journal: Br J Clin Pharmacol Date: 2002-01 Impact factor: 4.335
Authors: Bernard J Komoroski; Shimin Zhang; Hongbo Cai; J Matthew Hutzler; Reginald Frye; Timothy S Tracy; Stephen C Strom; Thomas Lehmann; Catharina Y W Ang; Yan Yan Cui; Raman Venkataramanan Journal: Drug Metab Dispos Date: 2004-05 Impact factor: 3.922
Authors: Soumen K Manna; Srujana Golla; Jaya Prakash Golla; Naoki Tanaka; Yan Cai; Shogo Takahashi; Kristopher W Krausz; Tsutomu Matsubara; Ilia Korboukh; Frank J Gonzalez Journal: Cancer Prev Res (Phila) Date: 2015-06-11