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Administration of Tobramycin in the Beginning of the Hemodialysis Session: A Novel Intradialytic Dosing Regimen

Osama Hussein Kamel Mohamed^*, Ihab M. Wahba, Suzanne Watnick^,, Sandra B. Earle, William M. Bennett^||,**, James W. Ayres^¶, and Myrna Y. Munar^**

^* Faculty of Pharmacy, Pharmaceutics Department, Cairo University, Cairo, Egypt; Division of Nephrology and Hypertension, Department of Medicine, Oregon Health & Science University, Portland, Oregon; Division of Hospital and Specialty Medicine, Portland Veterans Administration Medical Center, Portland, Oregon; Department of Pharmacy Practice, Findlay University School of Pharmacy, Findlay, Ohio; ^|| Solid Organ and Cellular Transplantation, Legacy Good Samaritan Hospital, Portland, Oregon; ^** Department of Pharmacy Practice, Oregon State University College of Pharmacy, Portland Campus at Oregon Health & Science University, Portland, Oregon; and ^¶ Department of Pharmaceutical Sciences, Oregon State University College of Pharmacy, Corvallis, Oregon

Correspondence: Dr. Myrna Y. Munar, Department of Pharmacy, Oregon State University College of Pharmacy, Portland Campus at Oregon Health & Science University, 3303 SW Bond Avenue, Mail Code CH12C, Portland, OR 97239. Phone: 503-494-5164; Fax: 503-494-8797; E-mail: munarm{at}ohsu.edu

Background: Aminoglycoside antibiotic efficacy is related to peak concentration (C_max) 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 C_max 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 C_max, 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 C_max 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.

Conclusions: Tobramycin administration during the first 30 min of hemodialysis results in similar C_max but lower AUC to conventional dosing, which may translate into comparable efficacy but lower toxicity.

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