Clinical pharmacology of cytarabine in patients with acute myeloid leukemia: a cancer and leukemia group B study.
The pharmacokinetics of cytarabine (ara-C) were determined in 265 patients with acute myeloid leukemia (AML) receiving ara-C (200 mg/m2 per day for 7 days as a continuous infusion) and daunorubicin during induction therapy. The mean (standard deviation) ara-C concentration at steady-state (Css) and systemic clearance (Cl) were 0.30 (0.13) microM and 134 (71) l/h per m2 respectively. Males had a significantly faster ara-C Cl (139 vs 131 l/h per m2, P = 0.025) than females. Significant correlations were noted between ara-C Cl and the pretreatment, peripheral white blood cell count (P = 0.005) and pretreatment blast count (P = 0.020). No significant differences in ara-C Css or Cl were noted in patients achieving complete remission compared with those failing therapy (P = 0.315, P = 0.344, respectively). No significant correlations were observed between ara-C pharmacokinetic parameters and several indices of patient toxicity. Our findings indicate that variability in ara-C disposition in plasma at this dosage level does not correlate with remission status or toxicity in patients with AML receiving initial induction therapy with ara-C and daunorubicin.
Fleming
R A
RA
Comprehensive Cancer Center, Wake Forest University, Winston-Salem, NC 27157-1082, USA.
Capizzi
R L
RL
Rosner
G L
GL
Oliver
L K
LK
Smith
S J
SJ
Schiffer
C A
CA
Silver
R T
RT
Peterson
B A
BA
Weiss
R B
RB
Omura
G A
GA
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D003561:Cytarabine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D003561:Cytarabine