Influence of hemodialysis on gentamicin pharmacokinetics, removal during hemodialysis, and recommended dosing.
OBJECTIVE
Aminoglycoside antibiotics are commonly used in chronic kidney disease stage 5 patients. The purpose of this study was to characterize gentamicin pharmacokinetics, dialytic clearance, and removal by hemodialysis and to develop appropriate dosing strategies. Design Setting, Participants, and Measurements: Eight subjects receiving chronic, thrice-weekly hemodialysis with no measurable residual renal function received gentamicin after a hemodialysis session. Blood samples were collected serially, and serum concentrations of gentamicin were determined.


RESULTS
Median (range) systemic clearance, volume of distribution at steady state, and terminal elimination half-life were 3.89 ml/min (2.69-4.81 ml/min), 13.5 L (8.7-17.9 L), and 39.4 h (32.0-53.6 h), respectively. Median (range) dialytic clearance, estimated amount removed, and percent maximum rebound were 103.5 ml/min (87.2-132.7 ml/min), 39.6 mg (19.7-43.9 mg), and 38.7% (0%-71.8%), respectively. Gentamicin dialytic clearance was statistically significantly related to creatinine dialytic clearance (r(2) = 0.52, P = 0.04), although this relationship is not likely to be strong enough to serve as a surrogate for gentamicin monitoring. The pharmacokinetic model was used to simulate gentamicin serum concentrations over a one-wk period.


CONCLUSIONS
In clinical situations where gentamicin is used as the primary therapy in a patient receiving hemodialysis with a CAHP hemodialyzer, conventional doses after each dialysis session are not as efficient at achieving treatment targets as predialysis dosing with larger doses.
Sowinski
Kevin M
KM
Department of Pharmacy Practice, Purdue University, W7555 Building, 1001 West 10th Street, Indianapolis, IN 46202-2879, USA. ksowinsk@iupui.edu
Magner
Stephanie J
SJ
Lucksiri
Aroonrut
A
Scott
Meri K
MK
Hamburger
Richard J
RJ
Mueller
Bruce A
BA
D000328:Adult; D000368:Aged; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D006435:Renal Dialysis
D005839:Gentamicins