Background hospitalized patients with serious\ninfections treated with aminoglycosides are at risk of\ndeveloping nephrotoxicity. Previous clinical studies have\nshown that the pharmacokinetics of aminoglycosides in\nhumans follow a circadian rhythm. Therefore, the time of\nadministration could have important clinical implications\nwith respect to the risk of developing aminoglycosideassociated\nnephrotoxicity in patients treated with once daily\ndosing regimens. Objective To examine the effect of the time\nperiod of administration on aminoglycoside exposure and\nthe incidence of nephrotoxicity in a large population of\nhospitalized patients with serious infections. Setting General\nward and intensive care unit of a teaching hospital. Method In\nthis retrospective cohort study, patients treated with intravenous\ntobramycin or gentamicin were eligible for inclusion.\nPatients were divided into three groups by time of administration:\nmorning, afternoon and night. Main outcome measure\nPharmacokinetic parameters and the incidences of\nnephrotoxicity were compared between the morning, afternoon\nand evening groups. Results 310 general ward and 411\nintensive care unit patients were included. No significant\ndifferences were found in patient characteristics between the\nmorning, afternoon and night groups. The time period of\nadministration did not affect aminoglycoside pharmacokinetics\nor the incidence of nephrotoxicity. Conclusion The\ntime of administration has no effect on the pharmacokinetics\nor nephrotoxicity of once daily dosed aminoglycosides in\nhospitalized patients. Consequently, we advise aminoglycosides\nto be administered as soon as possible in case of\n(suspected) severe hospital-acquired infections and subsequent\ndosages to be based on therapeutic drug monitoring\nto optimize the efficacy/toxicity balance.
Loading....