TY - JOUR
T1 - Administration of tobramycin in the beginning of the hemodialysis session
T2 - A novel intradialytic dosing regimen
AU - Kamel Mohamed, Osama Hussein
AU - Wahba, Ihab M.
AU - Watnick, Suzanne
AU - Earle, Sandra B.
AU - Bennett, William M.
AU - Ayres, James W.
AU - Munar, Myrna Y.
PY - 2007/7
Y1 - 2007/7
N2 - Background: Aminoglycoside antibiotic efficacy is related to peak concentration (Cmax) and postantibiotic effect, whereas toxicity is directly related to body exposure as measured by area under the serum concentration versus time curve (AUC). On the basis of pharmacokinetic simulation models, tobramycin administration during the first 30 min of high-flux hemodialysis achieves similar Cmax but significantly lower AUC and prehemodialysis concentrations compared with conventional dosing in the last 30 min of hemodialysis. Design, setting, participants, and measurements: To test this hypothesis, a pilot study in which five adult chronic hemodialysis patients who were undergoing high-flux dialysis received one dose of tobramycin 1.5 mg/kg intravenously during the first or last 30 min of hemodialysis was conducted. After a 1-mo washout period, patients crossed over to the other treatment schedule. Tobramycin serum concentrations were measured to determine Cmax, interdialytic and intradialytic elimination rate constants and half-lives, AUC, and clearance. Results: Tobramycin administration during the first and last 30 min of hemodialysis resulted in similar Cmax, of 5.63 ± 0.49 and 5.83 ± 0.67 mg/L (P > 0.05) but significantly lower prehemodialysis concentrations of 0.16 ± 0.09 and 2.44 ± 0.43 mg/L (P < 0.001) and AUC of 21.06 and 179.23 ± 25.84 mg/h per L (P < 0.001), respectively. Conc lusions: Tobramycin administration during the first 30 min of hemodialysis results in similar Cmax, but lower AUC to conventional dosing, which may translate into comparable efficacy but lower toxicity.
AB - Background: Aminoglycoside antibiotic efficacy is related to peak concentration (Cmax) and postantibiotic effect, whereas toxicity is directly related to body exposure as measured by area under the serum concentration versus time curve (AUC). On the basis of pharmacokinetic simulation models, tobramycin administration during the first 30 min of high-flux hemodialysis achieves similar Cmax but significantly lower AUC and prehemodialysis concentrations compared with conventional dosing in the last 30 min of hemodialysis. Design, setting, participants, and measurements: To test this hypothesis, a pilot study in which five adult chronic hemodialysis patients who were undergoing high-flux dialysis received one dose of tobramycin 1.5 mg/kg intravenously during the first or last 30 min of hemodialysis was conducted. After a 1-mo washout period, patients crossed over to the other treatment schedule. Tobramycin serum concentrations were measured to determine Cmax, interdialytic and intradialytic elimination rate constants and half-lives, AUC, and clearance. Results: Tobramycin administration during the first and last 30 min of hemodialysis resulted in similar Cmax, of 5.63 ± 0.49 and 5.83 ± 0.67 mg/L (P > 0.05) but significantly lower prehemodialysis concentrations of 0.16 ± 0.09 and 2.44 ± 0.43 mg/L (P < 0.001) and AUC of 21.06 and 179.23 ± 25.84 mg/h per L (P < 0.001), respectively. Conc lusions: Tobramycin administration during the first 30 min of hemodialysis results in similar Cmax, but lower AUC to conventional dosing, which may translate into comparable efficacy but lower toxicity.
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U2 - 10.2215/CJN.01600407
DO - 10.2215/CJN.01600407
M3 - Article
C2 - 17699484
AN - SCOPUS:34548827732
SN - 1555-9041
VL - 2
SP - 694
EP - 699
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 4
ER -