Место издания:Lippincott Williams & Wilkins Ltd United States
Первая страница:e-400
Последняя страница:e-400
Аннотация:Objective: Coenzyme Q10 (CoQ10) is recommended as a supplement to conventional therapy of congestive heart failure. Low solubility, poor absorption and high first-pass effect of CoQ10 limits a bioavailability of its oral dosage forms. To improve solubility and absorption the solubilization technology was used. Parenteral route allows creating higher plasma level of drug. The aim of the study was to evaluate absolute bioavailability and to estimate the tissue distribution of CoQ10 after intramuscular (i.m.) administration of solubilized CoQ10 aqueous solution.
Design and Methods: CoQ10 was administered i.m. (10 mg/kg) in male Wistar rats; the control rats received saline injection. Rats were sacrificed after administration in selected time intervals within 48 h. Tissue samples of left ventricle myocardium and liver were collected. Bioavailability of CoQ10 was investigated in separate set of experiments and calculated by comparing the areas under CoQ10 plasma concentration-time curves, plotted for intravenous and i.m. administration. The contents of CoQ10 were measured in plasma and tissue homogenates by HPLC with electrochemical detection. Statistical analysis was performed with two-tailed t-test.
Results: Calculated value of absolute bioavailability of CoQ10 was 17%. Myocardial content of CoQ10 was significantly (p<0,05) increased by 41%, 40%, 39%, 36%, 60% and 56% in 2, 4, 6, 12, 24, 48 h after CoQ10 solution administration, in comparison with control group. Hepatic CoQ10 level in 6, 12, 24, 48 h after CoQ10 solution administration was higher by 51% (p<0,05), 93% (p<0,01), 487% (p<0,01), 350% (p<0,01) respectively, than those in the control rats.
Conclusion: Intramuscular administration of solubilized CoQ10 aqueous solution provides early increase and maintaining its myocardial level at least for 48 h. The multiple increase of CoQ10 content in liver is subsequently serves as the reserve to support the plasma and myocardial levels. These findings experimentally prove the efficiency of this route of administration at acute cardiovascular events.