Oral Repeated-Dose Toxicity Studies of Coenzyme Q10 in Beagle Dogs

Abstract

To support phase III testing of coenzyme Q10 (CoQ10) in humans, we conducted pharmacokinetic and toxicology studies in beagle dogs. Following single gavage administration of CoQ10 at 600, 1200, 1800, or 2400 mg/kg per d no obvious dose response was observed in maximum concentration ( Cmax) or area under the curve (AUC) versus time curve at the 3 highest dosages. In a repeated-dose study of CoQ10 at 600, 1200, 1800, or 2400 mg/kg per d for 4 weeks, CoQ10 reached steady state in plasma by 2 weeks at all dosages. Both Cmax and AUC increased with increasing dosage of CoQ10. The highest plasma levels were recorded at 1800 mg/kg per d. In a 39-week chronic toxicity study of CoQ10 at 1200 and 1800 mg/kg per d or placebo, CoQ10 reached steady state in plasma by 13 weeks. Behaviors, blood chemistries, and detailed histopathology were normal. No deaths occurred. These results support the use of a 2400 mg/d dosage of CoQ10 in human clinical trials.