ATORVASTATIN IS NOT CATARACTOGENIC IN BEAGLE DOGS

Purpose. Atorvastatin (Lipitor(R)) 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 cata racts in dogs exposed to relatively high levels of the drugs for exten ded periods of time. The purpose of these studies was to assess the ca taractogenic 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 a ll studies. No clinical or histologic evidence of drug-induced catarac ts was found in any study. Lens biochemical analyses in the 13-week st udy revealed no statistically significant changes in lenticular weight , reduced or oxidized glutathione content, adenosine nucleotide conten t, glucose-6-phosphate dehydrogenase activity or phosphofructokinase a ctivity in any treatment group. Modest (11-17%) and transient decrease s 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 greater than or equal to 40 mg/kg. Conclusions. These studies d emonstrated that, in spite of marked reduction in serum cholesterol, a torvastatin was not cataractogenic in dogs at any tested dose. We conc lude that atorvastatin differs from other RIs in this regard.