Enhanced elimination of cyclophosphamide by high cut-off haemodialysis: single-dose pharmacokinetics in a patient with cast nephropathy
2018
High cut-off (HCO) haemodialysis removes free light chains in patients with multiple myeloma. This is possible as HCO dialysers allow clearance of molecules up to a molecular weight of 65 kDa. In contrast, high-flux dialysers, which are used in routine haemodialysis, only remove molecules up to a molecular weight of 20 kDa. Even though patients with advanced myeloma frequently need
dialysisand alkylating agents, drug dosing recommendations in this patient population are scarce at best or absent as for
cyclophosphamidedosing in patients with myeloma undergoing HCO
dialysis. Therefore, we aimed to determine pharmacokinetics of
cyclophosphamidein a 52-year-old man (height 172 cm, weight 80 kg) with cast nephropathy. Intermittent 4-hour haemodialysis was started ~6 hours after the end of a 70 min
cyclophosphamideinfusion containing 1700 mg of this drug. Blood/dialysate flow rates were 300/500 mL/hour, respectively. Peak concentration of
cyclophosphamidewas 24.7 mg/L. Using HCO
dialysis, plasma concentration of
cyclophosphamidedecreased from 10.8 mg/L to 3.7 mg/L during the treatment. The calculated whole blood dialyser clearance was 166 mL/min. HCO
dialysisled to a marked decrease of
cyclophosphamideresulting in a a 50% reduction in half-life as compared with the half-life before
dialysis. This removal has to be accounted for in dosing
cyclophosphamide.
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