title: 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 (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.
authors.affiliation: Neurology Clinical Trials Unit, Massachusetts General Hospital, 13th Street, Building 149, Room 2274, Charlestown, MA 02129, USA. mcudkowicz@partners.org
authors.forename: Padmaja
authors.initials: P
authors.lastname: Yerramilli-Rao
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.forename: Dai
authors.initials: D
authors.lastname: Watanabe
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
authors.forename: Elisabeth A de
authors.initials: EA
authors.lastname: Blieck
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Kitano
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hosoe
authors.forename: Iwao
authors.initials: I
authors.lastname: Funahashi
authors.forename: Merit E
authors.initials: ME
authors.lastname: Cudkowicz
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D005260:Female; D008297:Male; D018696:Neuroprotective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D018696:Neuroprotective Agents; D014451:Ubiquinone; C024989:coenzyme Q10