Effect of erythromycin and azithromycin on simvastatin - induced myositis in rats

ABSTRACT

Inhibitors of cytochrome P 3A4 are known to increase serum concentration of simvastatin and enhance its toxicity. This study is designed to evaluate the effects and compare erythromycin and azithromycin in their interaction with simvastatin. Sixty rats were used distributed equally to 6 groups. Control groups comprised a negative control [1[st] group], erythromycin [2[nd] group], azithromycin [3[rd] group] and simvastatin [4[th] group]. Simvastatin and erythromycin were concomitantly given to the 5th group while simvastatin azithromycin combination served as the 6[th] group. The drugs were orally administered at therapeutic doses of 18 mg/kg b.w. of erythromycin 9 mg/kg b.w. of azithromycin and 3.24 mg/kg b.w. of simvastatin. The drugs were given as single daily dose for 10 days. Assessment of serum creatinine, creatinine phosphokinase [CPK], aspartate aminotransferase [SGOT] and alanine aminotransferase [SGPT] was supplemented by skeletal muscle histopathology of rectus abdominis and quadriceps muscles of the thigh. A significant elevation of CPK was evident in all groups receiving simvastatin either alone or in combination with erythromycin or azithromycin. Compared with all other groups, the group of rats receiving erythromycin and simvastatin combination manifested a more significant elevation of CPK, SGOT, SGPT and serum creatinine. Biochemical results were supplemented with an evident myositis, degeneration and necrosis demonstrated at a higher rate in the simvatatin erythromycin combination group. No significant biochemical or pathologic change was noticed between simvastatin and azithromycin simvastatin combination group. As shown from this study azthromycin greatly enhanced the simvastatin - induced muscles toxicity, an interaction not demonstrated when azithromycin was co-administered with simvastatin. Erythromycin considered as an inhibitor to the cytochrome P 3A4, should be omitted and replaced by azithromycin whenever necessary in patients treated with simvastatin