Comparison of carboplatin pharmacokinetics between an anephric child and two children with normal renal function

Abstract

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.

Pharmacokinetically guided dosing of carboplatin and etoposide during peritoneal dialysis and haemodialysis

“…In the patients reported in this present study carboplatin was not cleared from plasma by peritoneal dialysis but was cleared by haemodialysis, confirming previous studies Koren et al, 1993;Motzer et al, 1990).…”

“…Although previous reports have monitored the pharmacokinetics of carboplatin in renal failure (Koren et al, 1993;Motzer et al, 1990) there has been only one report of targeted dosing of carboplatin (to an AUC of 6 mg ml-1 min) in a patient with ovarian carcinoma and renal failure (Chatelut et al, 1994). In the patients reported in this present study carboplatin was not cleared from plasma by peritoneal dialysis but was cleared by haemodialysis, confirming previous studies Koren et al, 1993;Motzer et al, 1990).…”

“…The complete formula takes account of both renal and non-renal clearance (Newell et al, 1993) al., 1994;Hall et al, 1994;Koren et al, 1993;Motzer et al, 1990). It was intended to wait 24 h before patient 2 was dialysed and his dose of carboplatin was calculated to give an AUC of 6 mg ml-' min assuming no effect from dialysis.…”

“…Renal impairment is predictive of toxicity in patients receiving etoposide (Clark et al, 1988), and a dose reduction of 50% has been suggested in all patients with poor kidney function (D'Incalci et al, 1986 Koren et al (1993) which underlines the importance of identifying a target AUC and then monitoring the achieved AUC.…”

Topotecan distribution in an anephric infant with therapy resistant bilateral Wilms tumor with a novel germline WT1 gene mutation

“…For optimal cure rates, these children beneWt from chemotherapy, before as well as after surgery. However, in anephric children, the management of adjuvant chemotherapeutic treatment has not been well described, illustrated by the fact that only scarce information is available on dose adjustment of various cytostatic drugs in case of renal failure in children [4,5,11,13,17,21].…”