Oral Repeated Dose Toxicity Studies of Coenzyme Q10 in Beagle Dogs

摘要

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 2400mg/kg/day no obvious dose response was observed in maximum concentration (Cmax) or area under the concentration versus time curve (AUC) at the three highest dosages. In a repeated dose study of CoQ10 at 600, 1200, 1800 or 2400mg/kg/day for four weeks, CoQ10 reached steady state in plasma by two weeks at all dosages. Cmax and AUC increased with increasing dosage of CoQ10. The highest plasma levels were recorded at 1800mg/kg/day. In a 39-week chronic toxicity study of CoQ10 at 1200, 1800mg/kg/day 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 2400mg/day dosage of CoQ10 in human clinical trials.