Toxicity, pharmacokinetics, and in vitro hemodialysis clearance of ifosfamide and metabolites in an anephric pediatric patient with Wilms' tumor.
OBJECTIVE
We evaluated the in vitro hemodialysis ratio and subsequent toxicity and pharmacokinetics of ifosfamide in an anephric patient with Wilms' tumor.


METHODS
An in vitro model was used to determine the extraction ratio of ifosfamide by dialysis. The toxicity and plasma concentrations of ifosfamide, chloroacetaldehyde, and 4-hydroxyifosfamide were then determined over 24 h after a single 1.6 g/m2 dose of ifosfamide. Plasma concentrations were also measured before and after ten dialysis sessions during four courses of ifosfamide therapy.


RESULTS
The in vitro hemodialysis model showed that ifosfamide was cleared with an extraction ratio of 86.7+/-0.5% and remained constant even at low concentrations of drug. The mean decrease in vivo following hemodialysis for ifosfamide, chloroacetaldehyde, and 4-hydroxyifosfamide were 86.9%, 77.2%, and 36.2%, respectively. The pharmacokinetic parameters for ifosfamide using model-independent methods were calculated: Vd = 0.23 l/kg, t1/2 = 4.8 h, and ClT = 3.30 l/h per m2. Ifosfamide-associated neurotoxicity was noted within hours of drug administration and improved rapidly following hemodialysis.


CONCLUSIONS
The results of our study suggest that the pharmacokinetics of parent ifosfamide may not be substantially altered in patients with renal failure. Hemodialysis was shown to remove ifosfamide, chloroacetaldehyde, and 4-hydroxyifosfamide from the blood stream. Hemodialysis was also shown to reverse ifosfamide-related neurotoxicity.
Carlson
L
L
Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas 75235, USA.
Goren
M P
MP
Bush
D A
DA
Griener
J C
JC
Quigley
R
R
Tkaczewski
I
I
Kamen
B A
BA
Weitman
S D
SD
D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics*; D007223:Infant; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008954:Models, Biological; D006435:Renal Dialysis; D009396:Wilms Tumor / Q000188:drug therapy / Q000378:metabolism*
D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide