The pharmacokinetics of the total pool of coenzyme Q(10) (Co(10)), its oxidized (ubiquinone) and reduced (ubiquinol, CoQ(10)H₂) 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)H₂ 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-part model (R² = 0.9932), while the corresponding curve of its oxidized form fits to the two-part 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 the 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.
Izuchena farmakokinetika obshchego pula koénzima Q10 (CoQ10), ego okislennoĭ (ubikhinon) i vosstanovlennoĭ (ubikhinol, CoQ10H2) form v plazme krovi krysy na protiazhenii 48 ch posle odnokratnogo vnutrivennogo vvedeniia rastvora soliubilizirovannogo CoQ10 (10 mg/kg). Opredelenie CoQ10 v plazme krovi provodili s pomoshch'iu vysokoéffektivnoĭ zhidkostnoĭ khromatografii so spektrofotometricheskim i kulonometricheskim detektirovaniem. Pokazano, chto na protiazhenii dvukh nedel' khraneniia pri -20°C v obraztsakh plazmy, otobrannoĭ v pervye minuty posle vnutrivennoĭ in"ektsii CoQ10, obshchee soderzhanie koénzima Q10 i dolia CoQ10H2 ostaiutsia neizmennymi. Kineticheskaia krivaia obshchego pula koénzima Q10 sootvetstvuet odnochastevoĭ modeli (R2=0,9932), ego okislennoĭ formy – dvukhchastevoĭ. Pokazano, chto uzhe v pervye minuty posle in"ektsii znachitel'naia chast' ubikhinona v plazme vosstanavlivaetsia, i spustia 7 ch kontsentratsiia ubikhinola stanovitsia preobladaiushcheĭ. Na fone snizheniia obshchego soderzhaniia koénzima Q10 dolia ubikhinola v plazme neuklonno vozrastaet i k kontsu pervykh sutok sostavliaet okolo 90%. Poluchennye rezul'taty dokazyvaiut sposobnost' organizma transformirovat' vysokie kontsentratsii okislennoĭ formy CoQ10 v éffektivnuiu antioksidantnuiu vosstanovlennuiu formu i obosnovyvaiut perspektivnost' razrabotki parenteral'nykh lekarstvennykh form CoQ10 dlia primeneniia v terapii ostrykh patologicheskikh sostoianiĭ.
Keywords: CoQ10; CoQ10H2; HPLC; coenzyme Q10; intravenous administration; pharmacokinetics; redox status; ubiquinol; ubiquinone.