Effective clearance of Ara-U the major metabolite of cytosine arabinoside (Ara-C) by hemodialysis in a patient with lymphoma and end-stage renal failure.
OBJECTIVE
We report that hemodialysis clears Ara-U from the blood after high-dose Ara-C treatment in a patient with lymphoma and end-stage renal failure.


METHODS
The patient received two doses of Ara-C 1 g/m(2) 24 h apart and was hemodialyzed at about 6 h after each dose and subsequently as per her usual dialysis schedule. Multiple blood samples were collected after dosing. Blood and dialyzate were also collected from the dialysis circuit during a second identical treatment cycle. Ara-C and its metabolite Ara-U in plasma and dialyzate were measured chromatographically, and the data subjected to pharmacokinetic analysis.


RESULTS
The distribution and elimination half-lives, steady-state volume of distribution and clearance values were 0.5 h, 7 h, 181 L and 307 l/h for Ara-C and 4.1 h, 34 h, 118 L and 2.64 l/h for Ara-U, respectively. The dialysis sessions immediately after the first and second doses cleared 39 and 52% (as Ara-U) of the respective Ara-C doses. Some 63% of Ara-U in plasma was extracted by dialysis. The patient showed no signs of neurotoxicity or other drug-related adverse effects.


CONCLUSIONS
Hemodialysis is very effective in clearing Ara-U from the plasma in renal failure, and this maneuver could easily be used routinely to prevent Ara-U accumulation and minimize adverse effects in patients with renal failure.
Radeski
Dejan
D
Haematology Department, Sir Charles Gairdner Hospital and Path West Laboratory Medicine, Hospital Avenue, Nedlands 6009, Western Australia. Dejan.Radeski@health.wa.gov.au
Cull
Gavin M
GM
Cain
Michael
M
Hackett
L Peter
LP
Ilett
Kenneth F
KF
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D001086:Arabinofuranosyluracil / Q000009:adverse effects / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003561:Cytarabine / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D020522:Lymphoma, Mantle-Cell / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control; D006435:Renal Dialysis
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D001086:Arabinofuranosyluracil