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. 2011:2011:207076.
doi: 10.1155/2011/207076. Epub 2010 Nov 28.

Effects of Flos carthami on CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats

Gaofeng Liu  1 , Yan Liu, Rui Liu, Feng Dong, Zhiren Zhang
Affiliations

Effects of Flos carthami on CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats

Gaofeng Liu et al. Evid Based Complement Alternat Med. 2011.

Abstract

Flos carthami is a traditional Chinese herbal medicine. Clinically, the Flos carthami Injection has been used concomitantly with other Western drugs and may be used concomitantly with β-blockers, such as metoprolol, to treat cerebrovascular and coronary heart diseases, in China. Metoprolol is a CYP2D6 substrate and is predominantly metabolized by this isozyme. However, we do not know whether there is an effect of Flos carthami on CYP2D6 and the consequences of such an effect. Concern is raised regarding the possible herb-drug interaction. In this report, the effects of Flos carthami on the activity of CYP2D6 in vivo and in vitro and on the pharmacokinetics of metoprolol, in rats, are investigated. To assess the inhibitory potency of Flos carthami, the concentration associated with 50% inhibition (IC(50)) of dextromethorphan metabolism was determined based on the concentration-inhibition curves. The inhibitory effect of Flos carthami on CYP2D6 was also compared with cimetidine in vitro. Flos carthami could significantly inhibit CYP2D6 in rats both in vitro and in vivo (P < .05) and could slow down the metabolic rate of metoprolol as suggested by prolonged t(1/2) (67.45%), by increased C(max) (74.51%) and AUC(0-∞) (76.89%). These results suggest that CYP2D6 is a risk factor when Flos carthami is administered concomitantly with metoprolol or other CYP2D6 substrates.

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Figures

Figure 1
Figure 1
HPLC chromatograms of urine of rats in vivo. (a) Blank group, (b) Flos carthami-treated group. DX: dextrophan (metabolite of dextromethorphan); DB: buprenorphine (internal standard); DM: dextromethorphan.
Figure 2
Figure 2
HPLC chromatograms of liver microsome of rats in vitro. (a) Blank group and (b) Flos carthami-treated group. DX: dextrophan (metabolite of dextromethorphan); DB: buprenorphine (internal standard); DM: dextromethorphan.
Figure 3
Figure 3
Linear regression of experimental data in vivo and in vitro.
Figure 4
Figure 4
The inhibition curve of Flos carthami on dextromethorphan metabolic rate (mean ± SD, n = 8). The concentration of Flos carthami was ranging from 0, 5, 10, 15, 20, 25, 30, to 45 mg/mL, respectively.
Figure 5
Figure 5
Comparison of the inhibitory activities of Flos carthami with cimetidine (mean ± SD; n = 8): (a) Blank group. (b) Flos carthami-treated group. (c) Cimetidine-treated group. *P < .05 versus blank group.
Figure 6
Figure 6
HPLC chromatogram of blood plasma of rats. (a) Metoprolol standard. (b) Bisoprolol standard.
Figure 7
Figure 7
Mean plasma concentration-time profiles of metoprolol in control group and Flos carthami-treated group.
Figure 8
Figure 8
Pharmacokinetics parameters of metoprolol (mean ± SD; n = 8); *P < .05.
Figure 9
Figure 9
CYP2D6-mediated herb-drug interaction between Flos carthami and metoprolol or other CYP2D6 substrates.
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References

    1. Bruno JJ, Ellis JJ. Herbal use among US elderly: 2002 National Health Interview Survey. Annals of Pharmacotherapy. 2005;39(4):643–648. - PubMed
    1. Ernst E. Herbal medicines—they are popular, but are they also safe? European Journal of Clinical Pharmacology. 2006;62(1):1–2. - PubMed
    1. Calapai G, Caputi AP. Herbal medicines: can we do without pharmacologist? Evidence-Based Complementary and Alternative Medicine. 2007;4(S1):41–43. - PMC - PubMed
    1. Firenzuoli F, Gori L. Herbal medicine today: clinical and research issues. Evidence-Based Complementary and Alternative Medicine. 2007;4(1):37–40. - PMC - PubMed
    1. Chavez ML, Jordan MA, Chavez PI. Evidence-based drug-herbal interactions. Life Sciences. 2006;78(18):2146–2157. - PubMed

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