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Pharmacokinetics of clodronate in haemodialysis patients
I Ala-Houhala1, H Saha, S Liukko-Sipi
1Tampere University Hospital, University of Tampere, Medical School, Finland.
Insights
Standard hemodialysis effectively removes clodronate, a bisphosphonate used for hypercalcemia. Dosage adjustments are not typically needed for hemodialysis patients, as clearance is similar to healthy individuals.
Area of Science:
- Pharmacology
- Nephrology
- Endocrinology
Background:
- Clodronate is a bisphosphonate essential for treating hypercalcemia.
- Renal excretion is the primary elimination pathway for clodronate.
- Understanding clodronate pharmacokinetics in hemodialysis patients is crucial for dosage adjustment.
Purpose of the Study:
- To determine the pharmacokinetic parameters of clodronate in hemodialysis patients.
- To assess the efficacy of hemodialysis in removing clodronate.
- To provide data for adjusting clodronate dosage in patients undergoing hemodialysis.
Main Methods:
- Intravenous infusion of 300 mg clodronate disodium in 10 hemodialysis patients.
- Analysis of clodronate in serum, urine, and dialysate using capillary gas chromatography-mass spectrometry.
- Calculation of pharmacokinetic parameters including hemodialysis clearance (CLD) and non-renal, non-dialysis clearance (CL(NRD)).
Main Results:
- Hemodialysis removed 53% (159 mg) of clodronate within 4 hours.
- Hemodialysis clearance (CLD) was 87.8 ± 16.2 ml/min, accounting for 84% of total serum clearance (CLtot).
- Non-renal, non-dialysis clearance (CL(NRD)) correlated positively with hyperparathyroidism severity and plasma intact parathyroid hormone (PTH) levels.
Conclusions:
- Standard hemodialysis effectively clears clodronate from circulation.
- Total clodronate clearance in hemodialysis patients is comparable to that in healthy subjects.
- The established dosing regimen for intravenous clodronate in hypercalcemia is applicable to hemodialysis patients, with skeletal deposition influenced by hyperparathyroidism severity.
Background:
Clodronate is a bisphosphonate used in the treatment of hypercalcaemia of various aetiologies. The major route of elimination of clodronate is renal excretion. The aim of the study was to derive data for the adjustment of dosage in haemodialysis patients.
Methods:
The pharmacokinetic parameters describing the fate of an intravenous infusion of 300 mg clodronate disodium were studied in 10 haemodialysis patients. Clodronate disodium in serum, urine and dialysate samples was analysed by capillary gas chromatography with mass-selective detection.
Results:
Of the 300 mg clodronate infused, 159 mg (53%) was excreted into dialysate within 4 h. Clearance by haemodialysis (CLD) was 87.8+/-16.2 ml/min, accounting for 84% of total serum clearance (CLtot). Non-renal, non-dialysis clearance (CL(NRD)) represents the removal of the drug via other routes than dialysis or kidneys. The greatest CL(NRD) was observed in patients with most severe hyperparathyroidism. There was a positive correlation between CL(NRD) and plasma intact PTH concentration.
Conclusions:
According to the present findings, standard haemodialysis removes clodronate effectively from the circulation, and total clearance in haemodialysis patients on a dialysis day is not very different from that in healthy subjects. The regimen of dosing intravenous clodronate in hypercalcaemia can also be used in haemodialysis patients. The portion of clodronate eliminated by routes other than via dialysate or kidneys, i.e. predominantly via skeletal deposition, was related to the severity of hyperparathyroidism.