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Elimination of intravenously administered ibandronate in patients on haemodialysis: a monocentre open study
Raoul Bergner1, Katja Dill, Dietmar Boerner
1Medizinische Klinik A, Klinikum der Stadt Ludwigshafen GmbH, Ludwigshafen, Germany. bergnerr@klilu.de
Insights
Ibandronate is effectively removed by hemodialysis, with levels nearing the limit of quantification after three sessions. A monthly 1 mg dose is unlikely to cause elevated levels in patients undergoing regular hemodialysis.
Area of Science:
- Pharmacology
- Nephrology
- Bone Metabolism
Background:
- Ibandronate inhibits osteoclast-mediated bone resorption, used for osteoporosis and metastatic bone disease.
- Pharmacokinetics of ibandronate in hemodialysis patients with renal osteopathy were previously unknown.
Purpose of the Study:
- To investigate the removal of ibandronate from plasma via hemodialysis.
- To determine the pharmacokinetics of ibandronate in patients with end-stage renal disease (ESRD) undergoing chronic hemodialysis.
Main Methods:
- 12 chronic hemodialysis patients with ESRD received 1 mg of intravenous ibandronate.
- Plasma ibandronate concentrations were measured pre- and post-dialyzer, and in dialysate during multiple dialysis sessions.
Main Results:
- Ibandronate plasma levels decreased significantly, with 78% reduction in the first 4 hours of dialysis.
- Hemodialysis removed approximately 36% of the administered ibandronate dose in the first session.
- Ibandronate dialysis plasma clearance was determined to be 92+/-19 ml/min.
Conclusions:
- Hemodialysis efficiently removes ibandronate, reducing plasma levels close to the quantification limit after three sessions.
- A standard monthly 1 mg ibandronate dose is unlikely to lead to accumulation in patients on thrice-weekly hemodialysis.
- Administer ibandronate after hemodialysis sessions in patients undergoing this treatment.
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 microg and using the mean difference in inflow/outflow (arteriovenous) concentration (A-V difference method) it was 371+/-132 microg. 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.
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