Aminoglycosides pharmacodynamics

Czock D, Giehl M, Keller F (2000) A concept for pharmacokinetic-pharmacodynamic dosage adjustment in renal impairment the case of aminoglycosides. Clin Pharmacokinet 38(4) 367—375. Erratum in Clin Pharma-cokinet 2000 39(3) 231... 

Integration of both pharmacokinetic and pharmacodynamic properties of an agent is important when choosing antimicrobial therapy to ensure efficacy and prevent resistance. Antibiotics may demonstrate concentration-dependent (aminoglycosides and fluoroquinolones) or time-depen-dent (/l-1 acta ms) bactericidal effects. 

Aminoglycosides are most useful for bacteraemias (especially Gram-negative septicaemia) since their volume of distribution is relatively low. With the exception of patients with renal failure or endocarditis they should be administered once-daily. This is because they exhibit a dose-dependent pharmacodynamic effect. This means that bactericidal activity is determined more by the peak plasma concentration than by the time that the plasma concentration is above the minimum required to achieve bacterial killing. The converse is true of p-lactams, which exhibit t/me-cfepenofent bacterial killing. 

Murry KR, McKinnon PS, Mitrayk B. Pharmacodynamic characterization of nephrotoxicity associated with once-daily aminoglycoside. Pharmacotherapy 1999 19 1252-1260. 

Zhanel, G.G. (1993) Once daily aminoglycoside dosing the result of research on antimicrobial pharmacodynamics. American Journal of Pharmaceutical Education, 56, 156-167. 

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