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  • Title: Herb-drug interactions: in vivo and in vitro effect of Shenmai injection, a herbal preparation, on the metabolic activities of hepatic cytochrome P450 3A1/2, 2C6, 1A2, and 2E1 in rats.
    Author: Xia CH, Sun JG, Wang GJ, Shang LL, Zhang XX, Zhang R, Peng Y, Wang XJ, Hao HP, Xie L, Roberts MS.
    Journal: Planta Med; 2010 Feb; 76(3):245-50. PubMed ID: 19774504.
    Abstract:
    Shenmai injection (SMI), a mixture of Radix Ginseng and Radix Ophiopogonis, is one of the most popular herbal medicinal products and is widely used for the treatment of coronary atherosclerotic cardiopathy and viral myocarditis. The purpose of this study was to investigate the effect of SMI, in vivo and in vitro, on the metabolic activities of hepatic cytochrome CYP450 3A1/2, 2C6, 2E1, and 1A2 in rats. After a single or multiple pretreatment with SMI, the rats were administrated intravenously a cocktail containing midazolam (1 mg/kg), diclofenac (0.5 mg/kg), theophylline (1 mg/kg), and chlorzoxazone (0.5 mg/kg) as probe substrates of rat CYP450 3A1/2, 2C6, 1A2, and 2E1, respectively. Single and multiple SMI pretreatment to rats resulted in a rise of 33.8 % (p < 0.01) and 25.6 % (p < 0.01) in AUC for midazolam, and an increase in AUC for diclofenac by 14.7 % (p < 0.05) and 31.2 % (p < 0.01), respectively. However, the pharmacokinetics of chlorzoxazone and theophylline in rats was not altered markedly. In rat liver microsomes, linear mixed-type inhibition of SMI against the enzyme activities of CYP3A1/2, CYP2C6, and CYP1A2 was shown with IC(50) values of 3.3 %, 2.0 %, and 3.1 % and K(i) values of 3.8 %, 1.5 %. and 1.9 %, respectively. These in vivo and in vitro results demonstrated that SMI had the potential to inhibit the activities of hepatic CYP3A1/2 and CYP2C6, but might not significantly affect CYP1A2 and CYP2E1-mediated metabolism in rats.
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