Pharmacological study of modified intermediate-dose cytarabine therapy in patients with acute myeloid leukemia.
BACKGROUND
Instead of the original intermediate dose (0.5 g/m2), a modified intermediate-dose 1-beta-D-arabinofuranosylcytosine (ara-C) therapy (1 g/m2, 1-h intravenous infusion) was pharmacologically studied in 11 leukemic patients.


METHODS
The concentrations of ara-C and its inactive metabolite, 1-beta-D-arabinofuranosyluracil (ara-U) in the plasma, urine and cerebrospinal fluid were determined using high performance liquid chromatography.


RESULTS
The plasma ara-C reached a peak (61.2 +/- 52.7 microM) that far surpassed the saturating level for intracellular activation of the drug. The plasma ara-U reached its peak (139.8 +/- 40.0 microM) and was maintained with a half-life of 277 +/- 76 min. About 60% of the administered drug was recovered, mainly as ara-U in urine within 12 h. In contrast to the original intermediate dose, the therapeutic ara-C levels (above 0.4 microM) persisted in the central nervous system. The therapy salvaged one relapsed leukemia patient with central nervous system involvement.


CONCLUSIONS
Modified intermediate-dose ara-C provides a sufficient plasma ara-C level with a concomitant therapeutic concentration in the cerebrospinal fluid.
Sutoh
Hidemasa
H
First Department of Internal Medicine, Fukui Medical University, 23, Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.
Yamauchi
Takahiro
T
Gotoh
Nobuyuki
N
Sugiyama
Masatoshi
M
Ueda
Takanori
T
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003561:Cytarabine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine