Elimination and clearance of pamidronate by haemodialysis (Brief Communication)

Abstract

Pamidronate (APD), a third-generation bisphosphonate, has proven to be useful in haemodialysis (HD) patients with ectopic calcifications and hypercalcaemia. Little is known about bisphosphonates clearance in patients undergoing HD. The authors' main objective was to study HD removal and clearance of APD. In total, 23 HD-requiring anuric end-stage renal disease (ESRD) adult individuals (12 men) aged 61.7 +/- 13 (mean +/- SD) years were admitted into the study. APD clearance and elimination were evaluated by (99m)Technetium APD (half-life 6 h). In total, 1 mg of labelled APD was injected via the arteriovenous graft prior to the start of HD. Blood samples were then drawn from the arterial (predialyser) and venous (postdialyser) lines of the extracorporeal circuit 2 h after the HD onset. In a subgroup of patients (n: 15) the dialysate was collected and quantified during the three initial HD hours. Venous APD concentrations (postdialyser) were 72 + 7% of arterial (predialyser) concentrations. Mean APD clearance was 69.3 + 16.6 mL/min, and mean APD extraction during dialysis session was 31.6 + 10.1%. In the present study involving HD-requiring anuric ESRD patients APD was successfully eliminated by HD. At the dose administered here none of the participants reported adverse events. APD is a potentially useful drug to be administered to HD-requiring ESRD patients, the understanding of its removal during HD as well as its dialytic clearance allows for a safer management of a drug that is usually eliminated by renal excretion.

Can bisphosphonates play a role in the treatment of children with chronic kidney disease?

“…Although elimination of pamidronate and ibandronate were shown to be significantly reduced in patients with severe CKD (GFR < 30 ml/min/1.73 m 2 ) compared with those with preserved kidney function, this was not thought to be clinically relevant [27,73,74]. In hemodialysis patients, effective clearance of clodronate, ibandronate and pamidronate has been reported [75][76][77]. In general, in patients with CKD stages 3-5 at least halving of the regular dosage and reduction of the frequency of administration is strongly recommended.…”

“…Once the bisphosphonate is immobilized to the skeleton, it may stick there for years and the biological half-life, albeit a drug-specific feature, is within the range of years rather than months [19,79]. However, in adult hemodialysis patients clearance of clodronate, ibandronate and pamidronate was shown to be quite effective [75][76][77].…”

Effects of Pamidronate and Calcitriol on the Set Point of the Parathyroid Gland in Postmenopausal Hemodialysis Patients with Secondary Hyperparathyroidism

“…Although pamidronate is well dialyzable [20], in order to prevent the development of marked hypocalcemia and/or oversuppression of osteoclasts [21] in patients with moderate SHP, a dose less than the regular dose was administered [18,22]. Pamidronate was administered intravenously as a single dose of 15 mg, diluted in 150 ml of 5% glucose solution and infused over 1 h in the last hour of HD [18].…”

Bisphosphonates in Chronic Kidney Disease; Balancing Potential Benefits and Adverse Effects on Bone and Soft Tissue

“…When given immediately before HD, clodronate was effectively removed, with 35% to 53% of the injected dose measured in dialysate (52,66). Ibandronate and pamidronate are also effectively removed by HD (67,68). One study in 16 HD dialysis patients assessed the pharmacokinetics and bone uptake of IV ibandronate, administered directly after dialysis thrice weekly (69).…”