Comparison of carboplatin pharmacokinetics between an anephric child and two children with normal renal function.
Carboplatin, a promising second generation platinum compound, is an effective antitumor drug and appears to be less nephrotoxic than cisplatin. We report comparative pharmacokinetics of carboplatin in an anephric child and two children with normal renal function. All three children were infused with carboplatin over 4 hours, the anephric child receiving 100 mg/m2 (25% of the dose received by the other two children). This dose was well tolerated and 18 days later the anephric patient received a second course of carboplatin at 50% of the regular dose received by the control patients. Following this dose the girl experienced severe pancytopenia and recovered with the use of GM-CSF, blood, and platelet transfusion. Blood samples were obtained at timed intervals for 24 hours in the control subjects and for 40 hours in the anephric patient. Plasma and plasma ultrafiltrates were analyzed for total and free platinum. The results show that elimination half-life of total platinum was 13 hours in the children with normal renal function and 42 hours in the anephric child following the 100 mg/m2 dose. The elimination T1/2 of free platinum was 8 hours in a child with normal GFR and 32 hours in the anephric child. In the anephric child the clearance of ultrafiltrable platinum was 10% of the normal total body clearance. We suggest that, in children with renal insufficiency, the dose of platinum derivatives should be carefully chosen, proportionally to the degree of renal impairment.
Division of Clinical Pharmacology, Hospital for Sick Children, Toronto, Ontario, Canada.
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G
Koren
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S
Weitzman
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J
Klein
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G
Moselhy
D001798:Blood Proteins / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D016190:Carboplatin / Q000097:blood / Q000493:pharmacokinetics*; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000502:physiology*; D009392:Nephrectomy; D010984:Platinum / Q000097:blood / Q000493:pharmacokinetics; D011485:Protein Binding; D006435:Renal Dialysis; D014462:Ultrafiltration; D009396:Wilms Tumor / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery
D001798:Blood Proteins; D010984:Platinum; D016190:Carboplatin