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Simvastatin‐tacrolimus and simvastatin‐cyclosporin interactions in rats
Author(s) -
Yamada Harumi,
Kotaki Hajime,
Sawada Yasufumi,
Iga Tatsuji
Publication year - 1998
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199807)19:5<279::aid-bdd101>3.0.co;2-q
Subject(s) - simvastatin , oral administration , creatine , pharmacology , creatine kinase , endocrinology , medicine , chemistry
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.