Pharmacokinetic Profiles of Coenzyme Q10: Absorption of Three Different Oral Formulations in Rats
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概要
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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 (CLtot) increased with a rise in the intravenous dose of CoQ10. The value of CLtot 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 wasnt 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 AUC0-24 value and absorption rate (Fa) than the other formulations (AUC0-24, 18876±6225 ng·h/ml; Fa, 0.15%). There was no difference in the values of AUC0-24 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.
著者
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Shibata Nobuhito
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Womens College of Liber
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Nishimura Asako
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Doshisha Women's College Of L
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Nishimura Asako
同志社女子大学 薬学部生物薬剤学
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Yanagawa Haruna
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Womens College of Liber
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Fujikawa Naoko
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Womens College of Liber
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Kiriyama Akiko
Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Womens College of Liber
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Kiriyama Akiko
Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts
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Yanagawa Haruna
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts
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Shibata Nobuhito
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts
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Fujikawa Naoko
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts
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