Overview of study groups.

Due to the critical impact of the ratios of sirolimus/cyclosporine and everolimus/cyclosporine on tissue metabolism as observed in previous studies, a checkerboard dosing scheme was used. Four rats were assigned to each group. All possible cyclosporine/sirolimus and cyclosporine/everolimus combinations of the following doses were tested: cyclosporine: 3.0, 6.0, 10.0 mg/kg/day; sirolimus and everolimus: 0.5, 1.5, 3.0 mg/kg/day. The “0.0 mg/kg/day” groups were given 1 mL vehicle solution (skim milk) instead of the active drug. “0.0/0.0 mg/kg/day” groups served as the vehicle controls.