Redox status and pharmacokinetics of coenzyme Q10 in rat plasma after its single intravenous administration
Е. И. Каленикова, Ekaterina Viktorovna Kharitonova, Evgeniya A. Gorodetskaya, Ольга Григорьевна Токарева, Medvedev Os
Abstract
Е. И. Каленикова, Ekaterina Viktorovna Kharitonova, Evgeniya A. Gorodetskaya, Ольга Григорьевна Токарева, Medvedev Os
Abstract
The pharmacokinetics of the total pool of coenzyme Q 10 (CoQ 10 ), its oxidized (ubiquinone) and reduced (ubiquinol, CoQ 10 H 2 ) forms have been investigated in rats plasma during 48 h after a single intravenous injection of a solution of solubilized CoQ 10 (10 mg/kg) to rats. Plasma levels of CoQ 10 were determined by HPLC with spectrophotometric and coulometric detection. In plasma samples taken during the first minutes after the CoQ 10 intravenous injection, the total pool of coenzyme Q 10 and proportion of CoQ 10 H 2 remained unchanged during two weeks of storage at −20°C. The kinetic curve of the total pool of coenzyme Q 10 corresponds to a one-compartment model ( R 2 = 0.9932), while the corresponding curve of its oxidized form fits to the two-compartment model. During the first minutes after the injection a significant portion of plasma ubiquinone undergoes reduction, and after 7 h the concentration of ubiquinol predominates. The decrease in total plasma coenzyme Q 10 content was accompanied by the gradual increase in plasma ubiquinol, which represented about 90% of total plasma CoQ 10 by the end of the first day. The results of this study demonstrate the ability of the organism to transform high concentrations of the oxidized form of CoQ 10 into the effective antioxidant (reduced) form and justify prospects of the development of parenteral dosage forms of CoQ 10 for the use in the treatment of acute pathological conditions.
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The pharmacokinetics of the total pool of coenzyme Q 10 (CoQ 10 ), its oxidized (ubiquinone) and reduced (ubiquinol, CoQ 10 H 2 ) forms have been investigated in rats plasma during 48 h after a single intravenous injection of a solution of solubilized CoQ 10 (10 mg/kg) to rats. Plasma levels of CoQ 10 were determined by HPLC with spectrophotometric and coulometric detection. In plasma samples taken during the first minutes after the CoQ 10 intravenous injection, the total pool of coenzyme Q 10 and proportion of CoQ 10 H 2 remained unchanged during two weeks of storage at −20°C. The kinetic curve of the total pool of coenzyme Q 10 corresponds to a one-compartment model ( R 2 = 0.9932), while the corresponding curve of its oxidized form fits to the two-compartment model. During the first minutes after the injection a significant portion of plasma ubiquinone undergoes reduction, and after 7 h the concentration of ubiquinol predominates. The decrease in total plasma coenzyme Q 10 content was accompanied by the gradual increase in plasma ubiquinol, which represented about 90% of total plasma CoQ 10 by the end of the first day. The results of this study demonstrate the ability of the organism to transform high concentrations of the oxidized form of CoQ 10 into the effective antioxidant (reduced) form and justify prospects of the development of parenteral dosage forms of CoQ 10 for the use in the treatment of acute pathological conditions.
Key concepts: Coenzyme Q10, Ubiquinol, Chemistry, Pharmacokinetics, Cofactor, Coenzyme Q – cytochrome c reductase, Pharmacology, Redox