Pharmacokinetic Profiles of Coenzyme Q 10: Absorption of Three Different Oral Formulations in Rats

Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, 610–0395, Kodo, Kyotanabe, Kyoto, Japan
Journal of health science (Impact Factor: 0.8). 08/2009; 55(4):540-548. DOI: 10.1248/jhs.55.540

ABSTRACT Pharmacokinetics and absorption profiles of coenzymeQ 10 (CoQ 10) 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 CoQ 10 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 CoQ 10 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 CoQ 10 . The value of CL tot increased in proportion to the intravenous dose. Three different formulations of CoQ 10 [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 CoQ 10 formulations because plasma concentrations of CoQ 10 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 formu-lations. After intraloop administration of CoQ 10 in the olive oil formulation, there were no significant differences in the plasma concentration of CoQ 10 , and the residual amounts of CoQ 10 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 CoQ 10 are nonlinear, and suggest the existence of a deep compartment for CoQ 10 accumulation in the intestine. Absorption of CoQ 10 from the intestine was very poor; however, a higher plasma concentration of CoQ 10 was achieved by an emulsion formulation using TPGS.

Download full-text


Available from: Asako Nishimura, May 07, 2015
35 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We examined pharmacokinetic (PK) and pharmacodynamic (PD) interactions between coenzyme Q 10 (CoQ 10) and nifedipine (NFP), which is a popular medicine for treating hypertension, and elucidated possible mechanisms for the interaction between CoQ 10 and NFP in rats. The mean plasma concentrations of NFP in rats after the oral administration of NFP (1 mg/kg) with CoQ 10 (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 CoQ 10 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 CoQ 10 pretreatment, and also no significant changes in the intestinal excretion of rhodamine 123 (Rho123) or NFP between with and without CoQ 10 were found. In contrast, the portal plasma concentration of NFP after intra loop administration in the presence of CoQ 10 (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 CoQ 10 over 10 mg/ml in the organic phase (n-hexane). From on an analysis of the absorbance spectrum, CoQ 10 showed a shift towards a longer wavelength in hydrophobic environments with NFP, suggesting that CoQ 10 reacts with NFP to form a charge-transfer complex due to a pi-cloud between them. In conclusion, it was found that CoQ 10 increases the oral bioavailability of NFP and that this interaction between NFP and CoQ 10 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 CoQ 10 , 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.
    Journal of health science 06/2010; 56(3):310-320. DOI:10.1248/jhs.56.310 · 0.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ubiquinone is an important biologically active compound in the living body. The determination of ubiquinone in human plasma is useful for the investigation of bioavailability of ubiquinone and for early diagnosis of several diseases. Therefore, we developed a high-performance liquid chromatography (HPLC) with chemiluminescence detection method for the analysis of ubiquinone in plasma samples. The method is based on luminol chemiluminescence detection of super oxide anion that is generated by the redox cycle reaction between ubiquinone and dithiothreitol. The HPLC system involved an octyl column with a mobile phase of methanol. Ubiquinone eluted from the column was mixed with dithiothreitol and luminol solutions simultaneously, and generated chemiluminescence was monitored by chemiluminescence detector. The calibration curve for standard ubiquinone solution was linear from 0.09 to 43.2 μg/mL (0.45-216 ng on column) with the correlation coefficient of 0.999, and the detection limit (S/N = 3) was 26 ng/mL (130 pg on column). Using the proposed HPLC method, the peak of ubiquinone in human plasma could be clearly detected on the chromatogram without any interference from plasma components.
    Analytical and Bioanalytical Chemistry 04/2011; 400(2):381-5. DOI:10.1007/s00216-011-4662-7 · 3.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bioavailability of a nanoparticulate formulation of coenzyme Q10 (NQ20), which has high stability in the water phase, was evaluated. The particle size was 188 nm, and the zeta potential value was between −38.8 and −44.8 mV at 4, 25, and 40°C in distilled water after eight weeks storage. Bioavailability of NQ20 was compared with a commercial coenzyme Q10 in oil and water phases as emulsified form using male Sprague-Dawley rats. After single oral administration of each coenzyme Q10 solution, the blood of rats was collected at 0, 1, 2, 3, 4, 5, 6, 9, and 12 h, and the concentrations of coenzyme Q10 were analyzed by high performance liquid chromatography. The plasma coenzyme Q10 levels at 1, 2, and 12 h were significantly higher when the rats were administered NQ20 compared to coenzyme Q10 in oil. The maximum plasma concentration (C max) and area under the concentration-time curve (AUC) values for NQ20 were 1.10±0.18 and 5.92±1.11 mM·h/mL, whereas the Cmax and AUC of coenzyme Q10 in oil were 0.79±0.07 and 5.30±0.62 mM·h/mL, respectively (p >0.05). Due to high absorbability and small particle size, NQ20 was found to have similar bioavailability to commercial coenzyme Q10 in the oil phase. Results indicate applicability of NQ20 in the food industry, particularly in beverages.
    Journal of the Korean Society for Applied Biological Chemistry 10/2012; 55(5). DOI:10.1007/s13765-012-2037-1 · 0.69 Impact Factor
Show more