Comparative pharmacokinetics of different coenzyme Q₁₀ formulations in Wistar rats: Superior bioavailability of phospholipid complex and lipid-encapsulated delivery systems

Background: Coenzyme Q₁₀ (CoQ₁₀) is a vital cofactor in the mitochondrial electron transport chain, mediating electron transfer between complexes I/II and III, and is essential for ATP synthesis. In addition to its bioenergetic role, CoQ₁₀ functions as a potent lipophilic antioxidant, protecting cellular membranes and lipoproteins against oxidative damage. Despite these benefits, its clinical application is constrained by poor oral bioavailability, attributed to its crystalline structure, high molecular weight, and extremely low aqueous solubility (<0.1 µg/mL). Several formulation strategies including nano emulsions, cyclodextrin complexes, liposomes, and phospholipid conjugates have been explored to enhance its absorption, but direct head-to-head comparative pharmacokinetic studies remain sparse. Objective: To evaluate and compare the pharmacokinetic profiles and relative bioavailability of five distinct CoQ₁₀ formulations standard CoQ₁₀, lipid-encapsulated CoQ₁₀, water-dispersible CoQ₁₀, phospholipid-complexed CoQ₁₀ in oil, and a marketed ubiquinone softgel following single-dose oral administration in Wistar rats. Methods: Fifty healthy adult Wistar rats (200–250 g) were randomized into five groups (n = 10 each). Group 1 received standard CoQ₁₀ (99%, 102.5 mg/kg); Group 2, lipid-encapsulated CoQ₁₀ (85%, 117.65 mg/kg); Group 3, water-dispersible CoQ₁₀ (40%, 250 mg/kg); Group 4, phospholipid-complexed CoQ₁₀ in oil (35%, 285.71 mg/kg); and Group 5, a marketed ubiquinone softgel (300 mg, 333.33 mg/kg). Blood samples were at 0, 0.5, 1, 2, 4, 8, 12, and 24 h via retro-orbital plexus. Plasma CoQ₁₀ levels were quantified using a validated LC–MS/MS method (lower limit of quantitation: 5 ng/mL). Non-compartmental pharmacokinetic analysis was performed using Phoenix WinNonlin to determine Cmax, Tmax, AUC₀–t, and relative bioavailability (Frel). Results: Pronounced formulation-dependent differences were observed. The phospholipid-complexed formulation (G4) achieved the highest systemic exposure (AUC₀–t: 2007.72 ± 109.03 ng·h/mL) and peak concentration (Cmax: 642.16 ± 24.51 ng/mL), with sustained plasma levels beyond 12 h. Lipid-encapsulated CoQ₁₀ (G2) produced comparable systemic exposure (1990.98 ± 45.39 ng·h/mL) with fast absorption (Tmax ~0.5 h). Both G4 and G2 demonstrated significantly greater exposure compared with standard CoQ₁₀ (G1; p < 0.05). Water-dispersible CoQ₁₀ (G3; AUC₀–t: 1567.91 ± 30.49 ng·h/mL) achieved faster absorption relative to G1 but yielded lower overall exposure, while the marketed soft gel (G5; AUC₀–t: 475.77 ± 4.01 ng·h/mL) exhibited the poorest systemic availability. Overall rank order of systemic exposure was: G4 > G2 > G1 > G3 > G5. Conclusion: Formulation technology is a key determinant of CoQ₁₀ pharmacokinetics. Phospholipid complexation provided the greatest improvement in systemic exposure, supporting its application in conditions requiring stable and sustained plasma levels. Lipid-encapsulated CoQ₁₀ provided rapid absorption and high systemic availability, suggesting potential clinical utility where fast onset is desirable. These findings provide a robust preclinical foundation for prioritizing advanced CoQ₁₀ delivery systems to optimize therapeutic efficacy and consumer adherence.