St. John's wort (SJW), a widely used herbal product, has been implicated
in drug interactions resulting from the induced expression of the
cytochrome P450 CYP3A4 isoform. In this study, we determined the effect of
SJW on the metabolism of irinotecan, a pro-drug of SN-38 and a known
substrate for CYP3A4. Five cancer patients were treated with irinotecan
(350 mg/m(2), intravenously) in the presence and absence of SJW (900 mg
daily, orally for 18 days) in an unblinded, randomized crossover study
design. The plasma levels of the active metabolite SN-38 decreased by 42%
(95% confidence interval [CI] = 14% to 70%) following SJW cotreatment with
1.0 micro M x h (95% CI = 0.34 micro M x h to 1.7 micro M x h) versus 1.7
micro M x h (95% CI = 0.83 micro M x h to 2.6 micro M x h) (P =.033,
two-sided paired Student's t test). Consequently, the degree of
myelosuppression was substantially worse in the absence of SJW. These
findings indicate that patients on irinotecan treatment should refrain
from taking SJW because plasma levels of SN-38 were dramatically reduced,
which may have a deleterious impact on treatment outcome