Nephrol Dial Transplant (2002) 17: 1281-1285
© 2002 European Renal Association-European Dialysis and Transplant Association
Elimination of intravenously administered ibandronate in patients on haemodialysis: a monocentre open study
1 Medizinische Klinik A, Klinikum der Stadt Ludwigshafen GmbH, Ludwigshafen, Germany and 2 Hoffmann-LaRoche, Grenzach-Wyhlen, Germany
Background. Ibandronate is an inhibitor of osteoclast-mediated bone resorption. This therapeutic effect is utilized in the treatment of osteoporosis and metastatic bone disease. The effect of ibandronate in patients on haemodialysis with renal osteopathy has not been studied since the pharmacokinetics of ibandronate under haemodialysis are unknown.
Methods. We analysed the removal of ibandronate from the plasma by haemodialysis in 12 chronic haemodialysis patients suffering from end-stage renal disease (ESRD). After intravenous administration of 1 mg ibandronate, the plasma concentration of ibandronate was determined in plasma samples drawn before entering (inflow) and after passing through (outflow) the haemodialyser, and in the dialysate at 1, 2, 3 and 4 h during the first haemodialysis session, and after 1 and 4 h during the second and third dialysis sessions.
Results. The back-extrapolated initial ibandronate plasma level was 38.9±15.9 ng/ml; this decreased during first haemodialysis (after 4 h) to 4.9±0.9 ng/ml and after two subsequent haemodialysis treatments to 0.38±0.16 ng/ml. Ibandronate concentration was reduced by 47% with every passage through the dialyser. The total decrease of ibandronate plasma concentration during the first 4 h of haemodialysis was 78% of plasma peak levels. The ibandronate dialysis plasma clearance was determined at 92±19 ml/min. The total amount excreted at the first dialysis using the recovery rate measure was 364±98 µg and using the mean difference in inflow/outflow (arteriovenous) concentration (A-V difference method) it was 371±132 µg. About 36% of the total amount of ibandronate administered (1 mg) was removed by the first dialysis treatment.
Conclusion. Ibandronate was efficiently removed by haemodialysis. After three haemodialysis sessions the ibandronate plasma levels were close to quantification limit. One monthly dose of 1 mg ibandronate would not result in elevated plasma levels in patients with ESRD on haemodialysis treatment three times a week. In haemodialysis patients, ibandronate should be administered after the haemodialysis session.
Keywords: haemodialysis; ibandronate; osteoclast-mediated bone resorption; plasma concentration
Correspondence and offprint requests to: Dr Raoul Bergner, Medizinische Klinik A, Klinikum der Stadt Ludwigshafen gGmbH, Bremserstrasse 79, D-67063 Ludwigshafen, Germany. Email: bergnerr{at}klilu.de
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