[Circadian variation of the nephrotoxicity induced in rats by bi-daily repeated administration of amikacin].

: We have studied the chrononephrotoxicity of amikacin during and after a prolonged treatment in rats. Animals received by intramuscular route a daily dose of 400 mg/kg (in two times) during 7 days at two different times (8.00 - 20.00 and 14.00 - 2.00). Large time-dependent variations in renal injury had been evidenced by several parameters and particularly by enzymuria. This injury is maximal when administration is made at 14.00 - 2.00. These data confirmed our results obtained in previous investigations with single daily injections and evidence that chrononephrotoxicity could permit an optimization of nephrotoxic drugs largely used in clinics.