Enhanced elimination of cyclophosphamide by high cut-off haemodialysis: single-dose pharmacokinetics in a patient with cast nephropathy

Abstract

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 65kDa. In contrast, high-flux dialysers, which are used in routine haemodialysis, only remove molecules up to a molecular weight of 20kDa. Even though patients with advanced myeloma frequently need dialysis and alkylating agents, drug dosing recommendations in this patient population are scarce at best or absent as for cyclophosphamide dosing in patients with myeloma undergoing HCO dialysis. Therefore, we aimed to determine pharmacokinetics of cyclophosphamide in a 52-year-old man (height 172cm, weight 80kg) with cast nephropathy. Intermittent 4-hour haemodialysis was started ~6hours after the end of a 70min cyclophosphamide infusion containing 1700mg of this drug. Blood/dialysate flow rates were 300/500mL/hour, respectively. Peak concentration of cyclophosphamide was 24.7mg/L. Using HCO dialysis, plasma concentration of cyclophosphamide decreased from 10.8mg/L to 3.7mg/L during the treatment. The calculated whole blood dialyser clearance was 166mL/min. HCO dialysis led to a marked decrease of cyclophosphamide resulting 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.