Aminoglycosides in intermittent hemodialysis: pharmacokinetics with individual dosing.
BACKGROUND
Data are limited on aminoglycoside pharmacokinetic differences between acute renal failure (ARF) and chronic kidney disease (CKD) or infection survival when maintaining peak and pre-hemodialysis serum concentrations between 7 and 10 and 3.5 and 5 mg/L, respectively.


OBJECTIVE
To report aminoglycoside pharmacokinetic observations in a consecutive series of patients receiving intermittent hemodialysis (IHD), including treatment impact of patient-specific dosing regimens.


METHODS
In this prospective study, all calculated pharmacokinetic parameters used concentrations drawn more than 12 hours after the initial dose and peak concentrations at least 2 hours after the dose. Analysis included pharmacokinetic parameters in stage 5 CKD, ARF, impact of the dialysis prescription, and treatment results of individualized dosing regimens lasting more than 4 days.


RESULTS
Consecutive patients with IHD (N = 167) receiving 216 courses of aminoglycosides were evaluated. The mean +/- SD volume of distribution was 0.39 +/- 0.15 L/kg ideal body weight, and elimination half-life during dialysis was 4.2 +/- 2.3 hours. The elimination half-life off IHD was 30% shorter in ARF (31.9 +/- 20.8 h) versus 45.7 +/- 24.2 hours in CKD (p < 0.001). Mean extrapolated peak concentrations and pre-IHD levels were 7.7 +/- 1.6 and 3.9 +/- 1.2 mg/L, respectively. A 91% treatment success rate was observed in 117 individualized treatment courses in 100 patients receiving greater than or equal to 5 days of aminoglycoside therapy.


CONCLUSIONS
A large variability in aminoglycoside pharmacokinetic parameters in IHD exists, with aminoglycoside elimination off IHD significantly faster in ARF. Individualized regimens using serum concentrations drawn in patients requiring treatment (non-synergistic) targeting peak concentrations of 7-10 mg/L and pre-hemodialysis serum concentrations of 3.5-5 mg/L appears successful for eradicating infections.
Dager
William E
WE
Department of Pharmaceutical Services, University of California Davis Medical Center, Sacramento, CA 95817-2201, USA. william.dager@ucdmc.ucdavis.edu
King
Jeff H
JH
D058186:Acute Kidney Injury / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy*; D000617:Aminoglycosides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D015897:Comorbidity; D005260:Female; D005839:Gentamicins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D006435:Renal Dialysis; D012737:Sex Factors; D013997:Time Factors; D014018:Tissue Distribution; D014031:Tobramycin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014031:Tobramycin