[Circadian variations of amikacin nephrotoxicity in rats]

We have studied the circadian variations in the nephrotoxicity of a single dose of a recently developed aminoglycoside, amikacin, in rats. Male rats placed in cages providing constant thermal conditions and lighted from 08:00 to 20:00 h were given a single intraperitoneal injection of 1.2 g/kg amikacin at different times of the 24 hour cycle (08:00, 14:00, 20:00 or 02:00). The study was carried out in October/November. Several parameters were monitored, including urinary excretion of gamma-glutamyl transferase, an enzyme found in the brush border of proximal tubule cells. The increase in urinary excretion of gamma-glutamyl transferase (expressed as a percentage) was found to vary according to the time of administration of amikacin. The highest GGT excretion occurred following administration of amikacin at 20:00 (484% +/- 62.75) and the lowest excretion, similar to that observed in controls, was found following administration at 14:00 (127% +/- 16.85). Thus, it seems that circadian variations in amikacin nephrotoxicity exist in rats. In a previous study we had found circadian variations in acute amikacin nephrotoxicity in mice. A thorough knowledge of these phenomena would improve our use of antibiotics in human clinical practice.