M K Scott1, B A Mueller, W R Clark. 1. Department of Pharmacy Practice, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN, USA.
Abstract
BACKGROUND: In comparison to conventional haemodialysis membranes, highly permeable membranes allow a broader spectrum of solute removal, including enhanced elimination of vancomycin (1448 Daltons). However, the mass transfer characteristics of vancomycin removal by highly permeable membranes have not been adequately assessed. An understanding of vancomycin's predominant dialytic mass transfer mechanism under a given set of operating conditions, including dialyser type and flow rates, may permit more accurate dosing of the drug. METHODS: We performed a mass transfer analysis of vancomycin removal by a high-flux dialyser, cellulose triacetate (CT). In a cross-over fashion with a 3-week washout between treatments, eight subjects received vancomycin 1000 mg (1) during the last hour of CT haemodialysis; or (2) after dialysis. Serial urea and vancomycin serum concentrations were used to assess dialytic removal. RESULTS: Dialysis removed 26.2% (mean; range 16-44%) of the administered vancomycin dose. While vancomycin removal and (Kt/V)urea were directly correlated (r = 0.88; P < 0.005), no correlation was observed between vancomycin removal and weight-normalized ultrafiltration rate. CONCLUSIONS: These findings suggest that for the CT dialyser and dialysis operating conditions employed in this study, vancomycin clearance was primarily mediated by diffusion. As such, these data challenge the general concept that convection is primarily responsible for the removal of solutes in the same molecular weight class as vancomycin during high-flux dialysis.
BACKGROUND: In comparison to conventional haemodialysis membranes, highly permeable membranes allow a broader spectrum of solute removal, including enhanced elimination of vancomycin (1448 Daltons). However, the mass transfer characteristics of vancomycin removal by highly permeable membranes have not been adequately assessed. An understanding of vancomycin's predominant dialytic mass transfer mechanism under a given set of operating conditions, including dialyser type and flow rates, may permit more accurate dosing of the drug. METHODS: We performed a mass transfer analysis of vancomycin removal by a high-flux dialyser, cellulose triacetate (CT). In a cross-over fashion with a 3-week washout between treatments, eight subjects received vancomycin 1000 mg (1) during the last hour of CT haemodialysis; or (2) after dialysis. Serial urea and vancomycin serum concentrations were used to assess dialytic removal. RESULTS: Dialysis removed 26.2% (mean; range 16-44%) of the administered vancomycin dose. While vancomycin removal and (Kt/V)urea were directly correlated (r = 0.88; P < 0.005), no correlation was observed between vancomycin removal and weight-normalized ultrafiltration rate. CONCLUSIONS: These findings suggest that for the CT dialyser and dialysis operating conditions employed in this study, vancomycin clearance was primarily mediated by diffusion. As such, these data challenge the general concept that convection is primarily responsible for the removal of solutes in the same molecular weight class as vancomycin during high-flux dialysis.