Pharmacokinetics of clodronate in haemodialysis patients

Background. Clodronate is a bisphosphonate used in the treatment of hyperca lcaemia of various aetiologies. The major route of elimination of clodronat e is renal excretion. The aim of the study was to derive data for the adjus tment of dosage in haemodialysis patients. Methods. The pharmacokinetic parameters describing the fate of an intraveno us infusion of 300 mg clodronate disodium were studied in 10 haemodialysis patients. Clodronate disodium in serum, urine and dialysate samples was ana lysed by capillary gas chromatography with mass-selective detection. Results, Of the 300mg clodronate infused, 159mg (53%) was excreted into dia lysate within 4 h. Clearance by haemodialysis (CLD) was 87.8+/-16.2ml/min, accounting for 84% of total serum clearance (CLtot). Non-renal, non-dialysi s clearance (CLNRD) represents the removal of the drug via other routes tha n dialysis or kidneys. The greatest CLNRD was observed in patients with mos t severe hyperparathyroidism. There was a positive correlation between CLNR D and plasma intact PTH concentration. Conclusions. According to the present findings, standard haemodialysis remo ves clodronate effectively from the circulation, and total clearance in hae modialysis patients on a dialysis day is not very different from that in he althy subjects. The regimen of dosing intravenous clodronate in hypercalcae mia can also be used in haemodialysis patients. The portion of clodronate e liminated by routes other than via dialysate or kidneys, i.e. predominantly via skeletal deposition, was related to the severity of hyperparathyroidis m.