Removal of clodronate by haemodialysis in end-stage renal disease patients

Background. Clodronate is a potent calcium-lowering drug. The effect of haemodialysis on clodronate pharmacokinetics is unknown. Methods. The removal of clodronate by haemodialysis was determined in 10 end-stage renal disease patients (ESRD). A 2-h infusion of 300 mg of clodronate was followed immediately by a 4-h haemodialysis. Vascular access was by AV fistula. A 1.5-m(2) cuprophane hollow-fibre dialyser was applied. Blood flow was 205 +/- 15 ml/min, dialysate flow 523 +/- 29 ml/min. Clodronate was determined by high-performance liquid chromatography in total collected dialysate, and in blood before and after the dialyser at initiation, 2 h, and 4 h of HD. Results. The initial predialyser serum concentration of clodronate was 13.6 +/- 4 mu g/ml. It decreased 4.9 +/- 0.5 mu g/ml and 2.6 +/- 0.5 mu g/ml at 2 h and 4 h respectively. The clearance of clodronate (86 +/- 10 ml/min) remained unchanged during HD. Clodronate in total collected dialysate per single 4-h HD was 105 +/- 16 mg (35% of injected dose). Conclusion. We conclude that clodronate is effectively removed from plasma by HD. The present data together with information provided by previous studies suggest that 300 mg of clodronate given as an 2-h infusion immediately prior to haemodialysis is an adequate dosage for ESRD patients.