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Pharmacokinetics of clodronate in peritoneal dialysis patients
H H Saha1, I O Ala-Houhala, S H Liukko-Sipi
1University of Tampere, Medical School, Tampere University Hospital, Finland.
Objective:
To study the pharmacokinetics of clodronate in patients on continuous ambulatory peritoneal dialysis (CAPD).
Design:
A single intravenous dose pharmacokinetic study.
Setting:
University hospital.
Patients:
Ten CAPD patients (3 female, 7 male, age 39-79 year, median 55).
Methods:
Clodronate disodium in serum, urine, and dialysate was collected for 24 hours and analyzed by capillary gas chromatography with mass-selective detection.
Results:
Only 7% of the infused dose of clodronate was eliminated through peritoneal dialysis during 24 hours. Clearance via CAPD (CL[CAPD]) was 2.4 +/- 0.6 mL/min, which was less than 10% of the total serum clearance (CL(tot), 26.0 +/- 19.3 mL/min). Even the kidneys were a more important route of elimination than CAPD in those patients with residual diuresis of more than 500 mL/24 hr. However, in all patients most of the clodronate serum clearance (77% +/- 13%) took place via routes other than peritoneal dialysis or kidneys, that is, via nonrenal-non-CAPD clearance (CL[NRD]). CL(NRD) most likely represents the part of the drug deposited in the skeleton. There was a positive correlation between CL(NRD) and the plasma intact parathyroid hormone concentration.
Conclusions:
CAPD removed clodronate poorly from the circulation. Most clearance took place via routes other than CAPD or kidneys. This CL(NRD) most likely represents the skeletal deposition of the drug, and this is related to the severity of hyperparathyroidism. When treating CAPD patients with hyperparathyroid bone disease, the administration of clodronate should be adjusted as in those subjects with severe renal failure.