A COMPARISON OF THE EFFECTS OF LOVASTATIN AND PRAVASTATIN ON UBIQUINONE TISSUE-LEVELS IN RATS

Treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reducta se inhibitors may reduce ubiquinone tissue levels, possibly resulting in decreased resistance to oxidative stress. Furthermore, the effects of several HMG-CoA reductase inhibitors may vary because of difference s in lipophilicity and tissue distribution. To answer these questions, the aim of this study was to compare the effects of 4 weeks of treatm ent with lovastatin or pravastatin (20, 40, or 80 mg/kg per day) on ub iquinone levels in mature male rats (n = 7 per dose). Ubiquinone-9 (Q( 9)) and ubiquinone-10 (Q(10)) levels in blood, myocardium, skeletal mu scle, and liver were measured by high-performance liquid chromatograph y at each dose level, and the groups were compared statistically. In b lood, decreases in Q(9) levels mere observed with both pravastatin and lovastatin (32% and 29%, respectively) and were not dose related. No significant effects were observed on Q(10) levels. In the myocardium, pravastatin caused a 20% decrease in Q(9) levels; the decrease plateau ed at the lowest dose (20 mg/kg per day). A dose-related decrease in Q (9) levels, which reached 40% at the highest dose, was observed with l ovastatin. Similar results mere obtained in Q(10) levels. In skeletal muscle, a trend toward lowered Q(9) levels was observed with both lova statin and pravastatin, although the decrease was not statistically si gnificant. No significant differences were observed in Q(10) levels. I n the liver a trend toward increased ubiquinone levels was observed, a lthough the increase was not statistically significant. Thus lovastati n;in and pravastatin tend to lower the concentration of ubiquinones in blood, myocardium, and skeletal muscle. The greater effect of lovasta tin in the myocardium can probably be attributed to higher tissue conc entrations of the drug because of its greater Lipid solubility. Becaus e of the proposed role of ubiquinone, both as a liposoluble antioxidan t and in mitochondrial bioenergetics, these findings may indicate that the use of some HMG-CoA reductase inhibitors may not be appropriate i n patients with preexisting pathologic conditions associated with decr eased levels of ubiquinones. Further studies in other animal species a re indicated to confirm the potential pharmacologic and therapeutic im portance of our findings.