Pamidronate distribution in pediatric renal and rheumatologic patients.
OBJECTIVE
To evaluate the distribution and elimination of pamidronate in a population of pediatric patients with renal and rheumatologic disease.


METHODS
Pamidronate whole blood levels were collected for the first 4 h after first exposure in 7 patients. The relationship between the rate of urinary excretion of pamidronate and bone formation or resorption was examined in 18 patients while receiving pamidronate at a total dose of 1 mg/kg/dose infused intravenously over a 4-h period. The urinary pamidronate clearances were correlated with renal function, calcium levels and measures of bone formation and resorption.


RESULTS
Pamidronate levels reached steady state concentrations of 0.9-1.5 microg/ml within 30 min and the clearance of the drug (mean+/-SE) from blood was 180.0+/-64.2 ml/kg/h with an elimination half-life of less than 1 h. The mean urinary excretion of 31.5+/-2.2% of the administered dose indicated that about 68% of the drug was incorporated into bone, confirming the uptake of pamidronate into bone was similar in pediatric patients compared to that previously reported for adults. Bone specific alkaline phosphatase, which is a marker for bone growth and formation, had significant correlation with the uptake of pamidronate into bone (p=0.002). No correlation was demonstrated with a marker for bone resorption (urinary N-telopeptide/creatinine ratio), or with creatinine clearance or calciuria when assessed 2 months after treatment.


CONCLUSIONS
Pamidronate at a dose of 1 mg/kg/dose every 2 months appears safe in the short term for pediatric patients, achieves relatively low whole blood pamidronate levels, and has similar skeletal uptake of pamidronate compared to adults.
Acott
Philip D
PD
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. Philip.acott@iwk.nshealth.ca
Wong
Jaime A
JA
Crocker
John F S
JF
Lang
Bianca
B
O'Regan
Patrick
P
Renton
Kenneth W
KW
D000293:Adolescent; D000469:Alkaline Phosphatase / Q000652:urine; D019540:Area Under Curve; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001842:Bone and Bones / Q000201:enzymology; D002118:Calcium / Q000652:urine; D002648:Child; D024042:Collagen Type I / Q000652:urine; D003404:Creatinine / Q000652:urine; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D015999:Multivariate Analysis; D000077268:Pamidronate; D010455:Peptides / Q000652:urine; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003404:Creatinine; D000469:Alkaline Phosphatase; D000077268:Pamidronate; D002118:Calcium