RLO: Pharmacokinetic and Pharmacodynamic Influences of Aminoglycoside Dosing


Traditionally, aminoglycosides have been given as a multiple daily dosage regimen, requiring the measuring of sufficient peak levels (to ensure efficacy) and low trough levels (to prevent toxicity). The factors influencing efficacy and nephrotoxicity have led to a move towards administering the total daily dose in one infusion (5 mg/kg, for example) in order to maximize the therapeutic peak while allowing an extended period with low aminoglycoside levels.

As administering the whole dose once a day will produce a huge peak, drug monitoring is simplified to just measuring trough levels.

Aminoglycosides are renally excreted, therefore a low trough result should be confirmed before dosing is continued in patients with known or likely renal impairment - for example, those over 65.

Studies have shown a reduction in nephrotoxicity, similar ototoxicity, and a trend towards improved efficacy and mortality with once daily administration. However, evidence of safety is lacking in certain circumstances: when treating endocarditis, in pregnancy, or when treating those with an abnormal volume of distribution (i.e. ascites or burns). In these groups, multiple daily dosing regimens are still used.

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