Simvastatin-tacrolimus and simvastatin-cyclosporin interactions in rats

Abstract

The effect of simvastatin (SV)‐tacrolimus (TL) and simvastatin‐cyclosporin (CyA) interactions on creatine phosphokinase levels and renal and hepatic function were investigated in rats. Animals were divided into seven groups; (1) SV (150 mg kg−1 oral) alone, (2) SV+TL (150 mg kg−1 oral+0.5 mg kg−1 intraperitoneal (i.p.)), (3) TL (0.5 mg kg−1 i.p.) alone, (4) SV+CyA (150 mg kg−1 oral+10 mg kg−1 oral), (5) CyA (10 mg kg−1 oral) alone, (6) control vehicle for oral administration, and (7) control vehicle for i.p. administration. A marked reduction in body weight and mortality was observed in the (SV+CyA) and (SV+TL) groups. Plasma creatine kinase levels in the (SV), (TL), (SV+CyA) and (SV+TL) groups, 7 days postadministration, were significantly higher compared with those before administration (p <0.05). The plasma urea nitrogen levels in the (TL), (SV+CyA) and (SV+TL) groups after 7 days of administration were significantly higher than those of the controls. In addition, a marked increase in the plasma levels of alanine and aspartate amino transferases were observed in the (SV+CyA) groups. © 1998 John Wiley & Sons, Ltd.

Tacrolimus/cerivastatin interaction study in liver transplant recipients

“…Regarding interactions between statins and tacrolimus, the only data reported so far have been a pronounced interaction observed for simvastatin in tacrolimus‐treated rats [10], similar to that described for cyclosporin [11]. Tacrolimus itself has been described to be primarily a CYP 3A4 substrate, and respective metabolic interactions e.g.…”