PHARMACOKINETICS OF CLODRONATE IN PERITONEAL-DIALYSIS PATIENTS

Objective:To study the pharmacokinetics of clodronate in patients on c ontinuous ambulatory peritoneal dialysis (CAPD). Design: A single intr avenous dose pharmacokinetic study. Setting: University hospital. Pati ents:Ten CAPD patients (3 female, 7 male, age 39 - 79 year, median 55) . Methods: Clodronate disodium in serum, urine, and dialysate was coll ected for 24 hours and analyzed by capillary gas chromatography with m ass-selective detection. Results: Only 7% of the infused dose of clodr onate was eliminated through peritoneal dialysis during 24 hours. Clea rance via CAPD (CLCAPD) was 2.4 +/- 0.6 mL/min, which was less than 10 % of the total serum clearance (CLtot, 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, i n all patients most of the clodronate serum clearance (77% +/- 13%) to ok place via routes other than peritoneal dialysis or kidneys, that is , via nonrenal-non-CAPD clearance (CLNRD). CLNRD most likely represent s the part of the drug deposited in the skeleton. There was a positive correlation between CLNRD and the plasma intact parathyroid hormone c oncentration. Conclusions: CAPD removed clodronate poorly from the cir culation. Most clearance took place via routes other than CAPD or kidn eys. This CLNRD 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 admini stration of clodronate should be adjusted as in those subjects with se vere renal failure.