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-m2 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 micrograms/ml. It decreased to 4.9 +/- 0.5 micrograms/ml and 2.6 +/- 0.5 micrograms/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.
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 diseasepatients (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-m2 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 micrograms/ml. It decreased to 4.9 +/- 0.5 micrograms/ml and 2.6 +/- 0.5 micrograms/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 ESRDpatients.
Authors: Serge Cremers; Matthew T Drake; F Hal Ebetino; John P Bilezikian; R Graham G Russell Journal: Br J Clin Pharmacol Date: 2019-02-28 Impact factor: 4.335