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Pharmacist Specialist, Department of Pharmaceutical Services, Davis Medical Center, University of California, Clinical Professor of Pharmacy, School of Pharmacy, University of California, San Francisco. Clinical Professor of Medicine, Davis School of Medicine, University of California. Department of Pharmaceutical Services, Davis Medical Center, University of California, 2315 Stockton Boulevard, Sacramento, California 95817-2201, fax 916/703-4031, william.dager{at}ucdmc.ucdavis.edu
Published Online, March 28, 2006. www.theannals.com, DOI 10.1345/aph.1G420
Methods. An aminoglycoside plasma concentration (Cp) was requested just prior to the start of EDD, once or twice during, immediately after, and one hour after completion of EDD. Additional serum concentrations were requested while patients were off hemodialysis to determine the elimination rate constant (k) and the volume of distribution (Vd) independent of dialysis. All Cp were drawn more than 18 hours after the first dose. Calculations assumed a linear, one compartment model, where k = (Ln Cp1/Cp2)/time between the measured Cp, elimination half-life using t1/2 = 0.693/k, and Vd = dose/(Cp extrapolated to the end of infusion using a Cp >2 h post dose —Cp trough).
Four consecutive critically ill patients with acute renal failure were evaluated while receiving either gentamicin or tobramycin during EDD. Dialysis blood flow during EDD was 200 mL/min with a dialysate rate of 300 mL/min. Observed pharmacokinetic parameters were calculated for the patient off hemodialysis and at different times after the start of hemodialysis (Figure 1). The intradialytic half-life we observed was slower, ranging from 5.0 to 7.2 hours, compared with rates (half-life 3.7 ± 0.8 and 70.1% total clearance) observed by Manley et al.,2 using a different form of extended hemodialysis in patients with end-stage renal disease, or as we had previously observed in our patients who received intermittent hemodialysis (half-life 4.8 ± 2.4 h, n = 31).2,3 Elimination was notably faster initially than toward the end of EDD therapy. As observed by Manley et al,2 no post-EDD rebound in aminoglycoside Cp occurred. The lack of rebound suggests that lower dialysis blood flow rates may be similar or slower than the diffusion of drug from the tissues to the plasma.
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Discussion. The aminoglycoside elimination half-life during EDD appears to be shorter initially. The total amount of the drug removed (46-62%), however, is similar to total aminoglycoside removal previously observed during 3-4 hours of intermittent hemodialysis at higher dialysis blood flow rates, but for half the duration. The apparent absence of notable rebound suggests no need to wait one hour after dialysis to draw an aminoglycoside Cp. More studies are needed to fully understand the variables and the extent of drug removal in EDD.
References
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