An understanding of vincristine (VCR) pharmacokinetics (PK) is important to achieve drug dosing that optimizes efficacy and minimizes toxicity. Limited information is available on the PK behavior of VCR in infants.

Objectives: To determine the PK of VCR in infants, and to compare the PK parameters of infants to those in older children.

Methods: A subset of 28 patients enrolled on the Pediatric Oncology Group 9407 infant leukemia study participated in this VCR PK study. PK samples were collected following the administration of VCR (0.05 mg/kg) i.v. push on week 1, day 1 of treatment. Twenty-eight patients, median age 7.1 months (range, 0.1–11.9 months) had blood samples collected for analysis of VCR concentrations at 5 minutes, and 0.5, 1, 4, and 24 h after drug administration. Samples were analyzed using a validated LC-MS method. A two-compartment model was fit to each patients data using Bayesian estimation (Adapt II software).

Conclusions: PK parameters in infants < and > 6 months of age were similar. CL in this population ranged from 7.8–31 ml/min/kg and was correlated with body weight, however only 25% of the variability in VCR CL could be accounted for by this variable. CL and t1/2 values are similar to those previously reported in older children. Evaluation of pharmacokinetic/pharmacodynamic correlation is ongoing.

Results:

VCR (mean ± SD)
AUC (mcg•hr/L ) 41.7 ± 19 
CL (ml/min/kg) 19.2 ± 6 
Vc (L/kg) 1.3 ± 1 
t 1/2 elimination (h) 17.1 ± 8.3 
Kcp (hr-1) 5.2 ± 1.7 
Kpc (hr-1) 0.3 ± 0.14 
VCR (mean ± SD)
AUC (mcg•hr/L ) 41.7 ± 19 
CL (ml/min/kg) 19.2 ± 6 
Vc (L/kg) 1.3 ± 1 
t 1/2 elimination (h) 17.1 ± 8.3 
Kcp (hr-1) 5.2 ± 1.7 
Kpc (hr-1) 0.3 ± 0.14 
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Topics:
acute lymphocytic leukemia, infant, pharmacokinetics, vincristine, drug dose, leukemia, toxic effect, child, software

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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