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Drugs containing coenzyme Q10 (CoQ10) in the oxidized (ubiquinone) or reduced forms (ubiquinol) are used to treat diseases associated with redox imbalance and are intended only for peroral administration. Parenteral solubilized forms of CoQ10 could fully reveal its therapeutic potential because of its low bioavailability. This study was aimed at comparing the pharmacokinetics and tissue distribution of CoQ10 upon intravenous administration of new dosage forms of ubiquinone and ubiquinol. Preparations (1% aqueous solutions with similar excipient compositions) were administered intravenously to rats (single dose, 30 mg/kg). Samples of blood, myocardium, brain, liver, and kidneys were taken for 8 d after administration using five rats for each time point. The CoQ10 content was determined by HPLC-EC. The AUC and Cl values were calculated. It was found that replenishment of the CoQ10 tissue content in individual organs was equally successful despite different total clearances of ubiquinol and ubiquinone, which implied they were equally effective upon intravenous administration.

The ability of i.v. injected ubiquinol to influence the concentration and redox state of CoQ10 (concentration ratio of ubiquinol to total CoQ10) in rat tissues was evaluated. The ubiquinol and total CoQ10 contents before and for 8 d after i.v. administration of an aqueous solution (1%) of solubilized ubiquinol drug substance at a dose of 30 mg/kg were determined using HPLC with electrochemical detection. It was demonstrated for the first time that i.v. administration of ubiquinol did not affect the redox state in myocardium and brain and gradually increased it in liver, regardless of CoQ10 concentration changes in the organs. The ubiquinol fraction of the total CoQ10 content in blood plasma was constant for a minimum of 2 d after administration and was the highest of all studied tissues. The redox state of CoQ10 in plasma and organs differed because ubiquinol was partially oxidized to the level of the organ endogenous redox equilibrium during the transfer.

The pharmacokinetics of ubiquinol in a new dosage form for intravenous injection were studied for the first time. Biexponential kinetic curves were found using HPLC with electrochemical detection in 48-h experiments in rats. The main pharmacokinetic parameters, i.e., area under the kinetic curves, elimination half-life, and total clearance, were calculated. The pharmacokinetics were nonlinear in the studied dose range (5, 10, and 20 mg/kg) with a higher dose corresponding to lower clearance. Multiple administrations increased the clearance, which implied extensive uptake of the drug into organ tissues that was required to manifest the protective effects of ubiquinol. Gradual oxidation of ubiquinol in blood plasma indicated that it was involved in endogenous redox processes.

The literature on the most frequently used methods for quantitative determination of coenzyme Q10 in biological materials was reviewed. HPLC in combination with electrochemical detection had the advantage among spectrophotometric, electrochemical, and chromatographic methods owing to high selectivity and sensitivity and the availability of modern detectors.

The various types of pharmacological activity of 4,5-dihydropyrazole derivatives are reviewed. Attention is focused on the influence of various substituents in the dihydropyrazole core on the pharmacological effects of these compounds.

The pharmacokinetics of ubidecarenone (CoQ10) in rat plasma and the kinetics of its organ levels were studied for the first time for 8-16 d after a single i.v. injection at a dose of 30 mg/kg. The pharmacokinetics followed a classical two-compartment curve. The main pharmacokinetic parameters for plasma (C 0, AUC 0→∞, K α, K el, t 1/2α, t 1/2el, Cl T, V d) and several organs (C max, T max, AUC 0→t , f tiss) were calculated. The results proved that CoQ10 injected i.v. rapidly attained and maintained for a long time high levels in plasma, myocardium, brain, liver, and kidneys. This was potentially important for treating acute ischemic states.

The pharmacokinetics of the promising antituberculosis drug dextrazide, the conjugate of polyaldehyde dextran with isonicotinic acid hydrazide, were studied using outbred ICR mice. The obtained results were indicative of two-phase dextrazide pharmacokinetics.

Methods of obtaining biotinylated oxidized dextran (BTOD) and procedures for pharmacokinetic studies of BTOD and biotinylated dextran (BTD) are described. The pharmacokinetics results showed that there are no differences in principle between the oxidized and unoxidized dextrans. All studied dextrans were characterized by two-phase pharmacokinetic profiles after intraperitoneal and subcutaneous administration.

Comparative dissolution kinetics were studied for ropinirole formulations using two media with pH 4.0: phosphate buffered solution (200 rpm) and citrate buffer (100 rpm). The study results showed that the components of the dissolution medium affected release profiles and the stability of the active ingredient even at identical pH. The optimum dissolution medium was citrate buffer solution, which provided the best release of active ingredient, with retention of the structure of the active substance.

The application of HPLC and UPLC techniques to the analysis of drugs in blood plasma during bioequivalence investigations and clinical monitoring was reviewed. Various methods of sample preparation, chromatography, and detection were considered and their specific features were pointed out.

A method for determining the number of aldehydes in dextran polyaldehyde (DPA) was proposed. The method was based on the production of the DPAconjugate with 2,4-dinitrophenylhydrazine, reaction of which with base formed a colored product. The developed method for quantitative determination of aldehydes was distinguished from others by its simplicity and high sensitivity. Results of physicochemical studies of DPA and their derivatives were presented in order to identify their structures and formation mechanism in the presence of KMnO4.

The dynamics of ubidecarenone (coenzyme Q10) levels in rat blood plasma and liver were monitored for two days after i.v. injection of solubilized ubidecarenone at doses of 10 and 30 mg/kg. The kinetic curves of the drug in plasma were exponential for both doses. The areas under the concentration—time curves differed by 8.6 times for the 10 and 30 mg/kg doses. Normalization to the dose did not superimpose them. The drug accumulated gradually in liver with the areas under the concentration—time curves differing by a factor of 4.4. These data indicated that ubidecarenone pharmacokinetics in plasma and liver were nonlinear after intravascular injection.

The bioavailability of coenzyme Q10(CoQ10) in various pharmaceutical formulations (solutions and tablets) containing solubilized CoQ10 in comparison to lipophilic powder of CoQ10 has been studied in rats. It is established that the bioavailability of solubilized CoQ10 in tablets and solution after peroral administration is higher than that of lipophilic CoQ10 powder. The time to reach peak CoQ10 concentrations in plasma was shorter for the solution of the solubilized form. Auxiliary swelling substances in tablets prolong and increase the absorption of CoQ10.