The effect of St John's wort on the pharmacokinetics of docetaxel.
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.


CONCLUSIONS
These results suggest that concomitant use of docetaxel and the applied SJW product should be avoided to prevent potential undertreatment of cancer patients.
Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands, andrew.goey@nih.gov.
Andrew K L
AK
Goey
Irma
I
Meijerman
Hilde
H
Rosing
Serena
S
Marchetti
Marja
M
Mergui-Roelvink
Marianne
M
Keessen
Jacobus A
JA
Burgers
Jos H
JH
Beijnen
Jan H M
JH
Schellens
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D000077143:Docetaxel; D005260:Female; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000494:pharmacology*; D043823:Taxoids / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D000928:Antidepressive Agents; D000970:Antineoplastic Agents; D010936:Plant Extracts; D043823:Taxoids; D000077143:Docetaxel; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human