Oral repeated-dose toxicity studies of coenzyme Q10 in beagle dogs

Int J Toxicol. 2012 Jan-Feb;31(1):58-69. doi: 10.1177/1091581811425256. Epub 2012 Jan 20.

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 (C(max)) 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 C (max) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Dogs
  • Female
  • Male
  • Neuroprotective Agents / blood
  • Neuroprotective Agents / pharmacokinetics
  • Neuroprotective Agents / toxicity*
  • Toxicity Tests, Acute
  • Toxicity Tests, Chronic
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / blood
  • Ubiquinone / pharmacokinetics
  • Ubiquinone / toxicity

Substances

  • Neuroprotective Agents
  • Ubiquinone
  • coenzyme Q10