文章基本信息

标题：Pharmacokinetic Profiles of Coenzyme Q10: Absorption of Three Different Oral Formulations in Rats
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作者：Asako Nishimura ; Haruna Yanagawa ; Naoko Fujikawa 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：2009
卷号：55
期号：4
页码：540-548
DOI：10.1248/jhs.55.540
出版社：The Pharmaceutical Society of Japan
摘要：Pharmacokinetics and absorption profiles of coenzymeQ₁₀(CoQ₁₀) from three different oral formulations were evaluated in rats. For the intravenous concentration-time data, a two-compartment open model fitted well. There were no significant changes in the values of the elimination rate constant at the terminal phase, and the half-life of CoQ₁₀ was estimated to be 7 to 8 hr. The values of intravenous area under the plasma concentration-time curve up to infinity (AUC_∞) increased with a rise in CoQ₁₀ dose (0.025 to 2.5 mg/kg); however, the AUC_∞ showed a nonlinear relationship with the administered dose. The total body clearance (CL_tot) increased with a rise in the intravenous dose of CoQ₁₀. The value of CL_tot increased in proportion to the intravenous dose. Three different formulations of CoQ₁₀ [olive oil solution (control), sub-nanosize particles and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-emulsion] were tested in rats. An appropriate compartment model wasn't adapted to the concentration-time data from orally administered CoQ₁₀ formulations because plasma concentrations of CoQ₁₀ from 10 to 24 hr after administration were markedly increased for all formulations tested. The TPGS-emulsion showed a significantly higher AUC_0-24 value and absorption rate (Fa) than the other formulations (AUC_0-24, 18876±6225 ng·h/ml; Fa, 0.15%). There was no difference in the values of AUC_0-24 and Fa between the control and subnano-particle formulations. After intraloop administration of CoQ₁₀ in the olive oil formulation, there were no significant differences in the plasma concentration of CoQ₁₀, and the residual amounts of CoQ₁₀ in the different parts of the intestinal loop (upper jejunum, lower jejunum, ileum) at the end of experiment were almost the same. These observations indicate that the pharmacokinetics of CoQ₁₀ are nonlinear, and suggest the existence of a deep compartment for CoQ₁₀ accumulation in the intestine. Absorption of CoQ₁₀ from the intestine was very poor; however, a higher plasma concentration of CoQ₁₀ was achieved by an emulsion formulation using TPGS.
关键词：coenzymeQ10;oral absorption;bioavailability;pharmaceutics;pharmacokinetics