Circadian variation in hepatic toxicity of the immunosuppressive agent “Mycophenolate Mofetil” in rats

Abstract

Immunosuppressive drugs may have varying toxicity or efficacy depending on the administration time. This study investigates whether the liver toxicity of the mycophenolate mofetil (MMF) varies according to the circadian dosing-time in rats. 300 mg/kg of MMF was injected by intraperitonal route to different groups of animals at four different circadian stages (1, 7, 13, and 19 h after light onset, HALO). Biochemical variable (transaminase, alkaline phosphatase) and histopathological examinations on liver section were performed. The results obtained showed that MMF treatment induced hepato-toxicity depending on the circadian time. A severe toxicity in the liver was observed when the drug was injected at 7 HALO. The data obtained indicate that the maximum of hepato-toxicity is observed when MMF was injected in the middle of the light-rest span of rats which is physiologically analogous to the end of the activity of the diurnal phase in human patients.