Drug Dosing Considerations in Alternative Hemodialysis Brian S. Decker, Bruce A. Mueller, Kevin M. Sowinski  Advances in Chronic Kidney Disease  Volume 14, Issue 3, Pages e17-e26 (July 2007) DOI: 10.1053/j.ackd.2007.03.004 Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 Schematic representation of a 2-compartment open-pharmacokinetic model in concert with drug removal by hemodialysis. Drugs are assumed to be removed from the central compartment either by hemodialysis or through endogenous means. Abbreviations: Cc, concentration of drug in the central compartment; Cp, concentration of drug in the peripheral compartment; Vc, volume of distribution of drug in the central compartment; Vp, volume of distribution of drug in the peripheral compartment; Cls, systemic clearance (sum of all endogenous clearances, such as renal and nonrenal clearance); ClDist, distribution clearance or intercompartmental clearance; Cldial, dialytic clearance. During hemodialysis, the hatched line is “turned on” with an indicator variable, in the absence of hemodialysis the hatched line is turned off. Advances in Chronic Kidney Disease 2007 14, e17-e26DOI: (10.1053/j.ackd.2007.03.004) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 2 Levofloxacin (A), gentamicin (B), and vancomycin (C) concentration-time profiles for the central (plasma) compartment in regimens A, B, and C (see Table 2 for dosing regimens). The profiles are shown for the intradialytic and interdialytic periods for 1 week after the administration of the first drug dose. Regimen A is conventional hemodialysis administered 3 times weekly for 4 hours each session. The times for the dialysis session were 44 to 48, 92 to 96, and 164 to 168 hours. Regimens B and C were daily hemodialysis administered 6 times weekly for 2 hours each session. The times for the dialysis session were 22 to 24, 46 to 48, 70 to 72, 94 to 96, 118 to 120, and 142 to 144 hours. Abbreviations: Vc, volume of distribution of drug in the central compartment; Vp, volume of distribution of drug in the peripheral compartment; Cls, systemic clearance; ClDist, distribution clearance or intercompartmental clearance; Cldial, dialytic clearance.24-26 All drugs were infused immediately after hemodialysis, according to manufacturer’s recommendations. Levofloxacin and vancomycin were administered as an intravenous infusion over 1 hour; gentamicin was administered as an intravenous infusion over 30 minutes. Abbreviations: LD, loading dose; MD, maintenance dose; HD, hemodialysis Conventional dialysis: regimen A, hemodialysis administered 3 times weekly at 44 to 48, 92 to 96, and 164 to 168 hours. Daily hemodialysis: regimens B and C, hemodialysis administered 6 times weekly at 22 to 24, 46 to 48, 70 to 72, 94 to 96, 118 to 120, and 142 to 144 hours. Advances in Chronic Kidney Disease 2007 14, e17-e26DOI: (10.1053/j.ackd.2007.03.004) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions