title: Atorvastatin is not cataractogenic in beagle dogs.
abstract: OBJECTIVE
  Atorvastatin (Lipitor) was developed as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase for treatment of serum lipid disorders. Other reductase inhibitors (RIs) induce cataracts in dogs exposed to relatively high levels of the drugs for extended periods of time. The purpose of these studies was to assess the cataractogenic potential of atorvastatin, when administered for up to 2 years in beagle dogs.
  
  
  METHODS
  Atorvastatin was administered at doses up to 150 mg/kg/day in 2-week, 13-week or 104-week studies. A 52-week interim sacrifice and a reversal group in which dosing was terminated at week 52 and the dogs sacrificed at week 64, was included in the 104-week study.
  
  
  RESULTS
  Serum cholesterol was significantly lowered in all studies. No clinical or histologic evidence of drug-induced cataracts was found in any study. Lens biochemical analyses in the 13-week study revealed no statistically significant changes in lenticular weight, reduced or oxidized glutathione content, adenosine nucleotide content, glucose-6-phosphate dehydrogenase activity or phosphofructokinase activity in any treatment group. Modest (11-17%) and transient decreases in lens protein, potassium and glucose content were noted in the 13-week study and at week 52 (glucose only) in the 104-week study, at the doses > or = 40 mg/kg.
  
  
  CONCLUSIONS
  These studies demonstrated that, in spite of marked reduction in serum cholesterol, atorvastatin was not cataractogenic in dogs at any tested dose. We conclude that atorvastatin differs from other RIs in this regard.
authors.affiliation: Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Co., Ann Arbor, MI, USA. rober04@aa.wl.com
authors.forename: D G
authors.initials: DG
authors.lastname: Robertson
authors.forename: E R
authors.initials: ER
authors.lastname: Urda
authors.forename: C E
authors.initials: CE
authors.lastname: Rothwell
authors.forename: K M
authors.initials: KM
authors.lastname: Walsh
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000069059:Atorvastatin; D002386:Cataract / Q000139:chemically induced*; D002784:Cholesterol / Q000097:blood; D004285:Dogs; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin