EFFECTS OF HMG-COA REDUCTASE INHIBITORS ON SKELETAL-MUSCLES OF RABBITS

This study was undertaken to evaluate the potential of HMG-CoA reducta se inhibitors, pravastatin sodium (hereafter abbreviated to pravastati n) and simvastatin, for induction of myopathy and influence on the ubi quinone content of skeletal and cardiac muscles and other tissues in t he rabbit. Both drugs were administered orally to New Zealand White ra bbits (n = 5) at the dose of 50 mg/kg per day for 14 days. Serum chole sterol levels in the pravastatin- and simvastatin-treated groups were reduced significantly by 47% an 58% on day 14 (P < 0.05), respectively , as compared with the control group, but the difference between the t wo treatment groups was not significant. In animals of the simvastatin -treated group, abnormal elevations of creatine kinase (CK) and lactat e dehydrogenase (LDH) levels were observed, in association with severe lesions in skeletal muscles, but not cardiac muscle. The ubiquinone c ontent in skeletal muscle in this treatment group was not affected, ev en in the muscles that had severe lesions, whereas that in liver and c ardiac muscle was significantly reduced compared with the control grou p. The results suggest that there is no direct correlation between myo pathy and the decrease of obiquinone content in skeletal muscles. In c ontrast, the animals in the pravastatin-treated group did not show any changes in CK and LDH levels, ubiquinone content in liver and muscles , or in histopathological features of muscle fibers. The difference be tween the adverse effects seen with the two drugs could be attributed to physicochemical properties: simvastatin permeates the plasma membra ne because of its hydrophobic nature, whereas pravastatin does not, be cuase it is hydrophilic.