Key result
Hypericum perforatum reduces ivabradine exposure by ~62% in healthy volunteers.
Why the study?
The effects of the CYP3A4 inducer Hypericum perforatum on the pharmacokinetics of ivabradine were not well characterized.
Does Hypericum perforatum alter the pharmacokinetics of ivabradine in healthy volunteers?
Does Hypericum perforatum alter the pharmacokinetics of ivabradine in healthy volunteers?
Absolute Event Rate: 43.7% vs 114%
p-value: p=<.01
Hypericum perforatum significantly decreases the plasma concentration and AUC of ivabradine, consistent with CYP3A4 induction.
May reduce ivabradine efficacy with Hypericum perforatum co-use; leaves open confirmation and dose guidance in patients.
The effects of the CYP3A4 inducer, Hypericum perforatum, on the pharmacokinetics of a single oral dose of ivabradine were assessed. An open-label, 2-period, nonrandomized, phase-I, pharmacokinetic interaction design was used. Twelve healthy volunteers received a single oral dose of ivabradine (10 mg) followed by H perforatum (300 mg orally, 3 times a day) for 14 days, combining the last dose with another single dose of ivabradine. Pharmacokinetic data for ivabradine (S16257) and its main active metabolite (S18982) prior to and after the administration of H perforatum were analyzed. After repeated administration of H perforatum, highest observed concentration in plasma (C(max)) and area under the concentration-time curve (AUC) were significantly decreased for ivabradine (32.7 +/- 16.6 vs 15.4 +/- 7.0 ng/mL, P < .01; 114 +/- 39.1 vs 43.7 +/- 12.0 ng x h/mL, P < .01, respectively), and for S18982 (C(max), 6.8 +/- 3.7 vs 5.1 +/- 2.0 ng/mL, P < .05; AUC, 56.2 +/- 23.4 vs 38.3 +/- 25.1 ng x h/mL, P < .01). Tendencies toward shorter time to C(max) and lower apparent terminal half-life values were found. Pharmacokinetic results are consistent with an induction of ivabradine metabolism by H perforatum.
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Portolés et al. (2006) studied Healthy volunteers (n=12). Hypericum perforatum vs. Ivabradine alone (baseline prior to H perforatum) was evaluated on Area under the concentration-time curve (AUC) for ivabradine (p=<.01). Repeated administration of Hypericum perforatum significantly decreased the maximum plasma concentration and AUC of ivabradine in healthy volunteers (P < .01).
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