文章基本信息

标题：Pharmacokinetic Interaction between Nifedipine and Coenzyme Q10 in Rats: A New Type of Drug-Supplement Interaction
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作者：Asako Nishimura ; Mari Fujimura ; Fuyuka Hasegawa 等
期刊名称：Journal of Health Science
印刷版ISSN：1344-9702
电子版ISSN：1347-5207
出版年度：2010
卷号：56
期号：3
页码：310-320
DOI：10.1248/jhs.56.310
出版社：The Pharmaceutical Society of Japan
摘要：We examined pharmacokinetic (PK) and pharmacodynamic (PD) interactions between coenzyme Q₁₀ (CoQ₁₀) and nifedipine (NFP), which is a popular medicine for treating hypertension, and elucidated possible mechanisms for the interaction between CoQ₁₀ and NFP in rats. The mean plasma concentrations of NFP in rats after the oral administration of NFP (1 mg/kg) with CoQ₁₀ (75 mg/kg) were increased over the study period and the area under the plasma concentration-time curve (AUC), showed a 1.47-fold increase compared with that of the control. Rats that received NFP with CoQ₁₀ showed a continuous decrease in the mean blood pressure over the study period compared with the control. There were no significant changes in the PK parameters of NFP after intravenous administration (1 mg/kg) between with and without oral CoQ₁₀ pretreatment, and also no significant changes in the intestinal excretion of rhodamine 123 (Rho123) or NFP between with and without CoQ₁₀ were found. In contrast, the portal plasma concentration of NFP after intra loop administration in the presence of CoQ₁₀ (75 mg/kg) showed a 1.6-fold increase in the AUC value compared with that of the control. As for physicochemical properties, the partition coefficient of NFP showed a marked increase in the presence of CoQ₁₀ over 10 mg/ml in the organic phase (n-hexane). From on an analysis of the absorbance spectrum, CoQ₁₀ showed a shift towards a longer wavelength in hydrophobic environments with NFP, suggesting that CoQ₁₀ reacts with NFP to form a charge-transfer complex due to a pi-cloud between them. In conclusion, it was found that CoQ₁₀ increases the oral bioavailability of NFP and that this interaction between NFP and CoQ₁₀ is not caused by metabolism via cycochrome P450 (CYP) 3A in the liver or intestine or by the inhibition of P-glycoprotein function, by the physicochemical interaction between them. Therefore, the solubility of NFP in a hydrophobic environment could be enhanced by forming a charge-transfer complex with CoQ₁₀, and it is considered that NFP deviating from a charge-transfer complex may migrate to the blood circulation from the intestinal tract. This mechanism of interaction is considered a new type of drug-supplement interaction.
关键词：nifedipine;coenzyme Q10;oral absorption;drug-drug interaction;pharmacokinetics;pharmacodynamics