ADMINISTRATION OF AMINOGLYCOSIDES TO HEMODIALYSIS-PATIENTS IMMEDIATELY BEFORE DIALYSIS - A NEW DOSING MODALITY

We describe a new modality for administering aminoglycosides to hemodi alysis (HD) patients, namely, a modification of the once-daily regimen which consists of administering the aminoglycosides over 60 min by dr ip infusion just before each HD session, with a preplanned peak concen tration being reached at the beginning of the session and then with a rapidly decreasing concentration being achieved by the start of HD. Th e area under the concentration-time curve (AUG), i.e., the accumulatio n of the drug in the body, is thus minimized by this modality. Arbekac in (ABK) was given at a dose of 2 mg/kg of body weight to 10 HD patien ts infected with methicillin-resistant Staphylococcus aureus (MRSA) fo r 2 seeks (six sessions in total), resulting in the complete disappear ance of MRSA in 5 patients, A high rate of elimination of ABK was atta ined for each patient while the patient was on HD (range, 0.20 to 0.42 h(-1); mean 0.28 +/- 0.08 h(-1)) by using high-performance dialyzers provided with membranes made of either polymethylmethacrylate, cellulo se triacetate (CTA), or ethylene vinyl alcohol. The best results were obtained with the CTA membrane, as revealed by the overall mass transf er coefficient (K-0), The AUC in the simulation model for the variatio n in the serum ABK concentration in this modality was calculated to be 40% of that of the conventional post-HD dosing modality, suggesting t hat a much higher dose could be administered to HD patients who receiv e HD thrice weekly (4 h per session), giving, e.g., 4 mg/kg initially and before the ED sessions, when there is an interval of 68 h from HD session to HD session, and giving 2 mg/kg before the other sessions.