Simvastatin-tacrolimus and simvastatin-cyclosporin interactions in rats.
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.
Yamada
H
H
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Kotaki
H
H
Sawada
Y
Y
Iga
T
T
D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D004347:Drug Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D016559:Tacrolimus / Q000008:administration & dosage / Q000633:toxicity*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019821:Simvastatin; D003402:Creatine Kinase; D016559:Tacrolimus