Relative bioavailability of different coenzyme Q10 formulation for pediatric use: Preliminary study

SAMASSA, P; MARTINEFSKI M; CONTIN M; LUCANGIOLI S.; BUONTEMPO F; TRIPODI V.

Congreso; 2° Reunion Internacional de Ciencias Farmaceuticas; 2012

Introduction Coenzyme Q10 (CoQ10) deficiency is involved in mitochondrial, cardiological and degenerative muscle and neuronal diseases. Most patients with these deficiencies have shown clinical improvement with oral CoQ10 supplementation specially if it is administered during chilhood. Crystalline powder CoQ10 formulations are often of poor intestinal absorption. It is well known that CoQ10 bioavailability depends mostly on the drug release system used, thus formulations containing dissolved drug are the most bioavailable ones (1-3). On the other hand, in the case of pediatric patients, the development of pharmaceutical formulations is a unique challenge specially in children with difficulty swallowing. Thus, liquid formulations rather than solid dosage forms are preferred for oral administration to children. In order to increase the bioavailability of CoQ10, facilitate its administration in pediatrics and therefore increase the therapeutic efficacy, we have previously developed an oil-in-water (O/W) liquid emulsion of CoQ10 with proved stability and safe when narrow dose adjustment is required (4). The objective of this work is to establish the relative bioavailability of this new developed liquid formulation in comparison to the solid CoQ10 formulation. Materials and Methods It was conducted a preliminary study. Five healthy male and female subjects participated in a double-blind, consecutive, controlled, single-oral low dose (60 mg) bioavailability study. The same group was administered with both formulations after a wash out of 15 days. Plasma concentration of CoQ10 was determined at baseline and at various intervals after administration over a 384-hour period. To compare bioavailability, maximum concentration (Cmax),  the time of its occurrence (Tmax) and area under curve from 0 to last time analized (AUCt) were assessed. Plasma concentrations were determined using a micro HPLC method previously developed (5). Analysis of variance (ANOVA) and t-tests were performed to evaluate significant differences between two formulations. Results The kinetic profiles of both CoQ10 preparations revealed a same 2-peak plasma concentration-time course (t6 and t24). While there was no difference in the Tmax between the two formulations, highest Cmax values were seen after liquid CoQ10 formulation (t6: 0.42 ±0.05 vs 0.34 ±0.02 µM and t24: 0.47 ±0.07 vs 0.36±0.01 µM, mean±SEM, p<0.05). The AUCt (µM x h)±SEM were 48.1±4.6 vs 36.1±4.5 for liquid and solid formulation, respectively (p<0.05). The relative bioavailability calculated using the AUCt values was 133.3%. Conclusions The data presented suggests that O/W emulsion of CoQ10  improves the enteral absorption and the bioavailability of CoQ10 in humans and justifies to continue the study in a higher number of healthy volunteers.