J. A. Tolbert,1 G. L. Kearns,1 S. M. Abdel-Rahman,1 S. J. Weir,2 J. S. Leeder,1 K. A. Neville1; 1Division of Clinical Pharmacology, Children's Mercy Hospital and the Department of Pediatrics, University of Missouri-Kansas City, Kansas City, MO, 2Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS

BACKGROUND: A liquid formulation of 6-MP (20 mg/ml) was recently FDA approved for children based only on adult data. We examined the PK of 2 liquid formulations in children with Acute Lymphoblastic Leukemia.
METHODS: 22 children (6-17 yrs) participated in a randomized, crossover study. All received a 50 mg oral 6-MP tablet. Group 1 (n=11; 5 males; 9.0±2.4 yr) also received a 5 mg/ml liquid and Group 2 (n=11; 5 males; 9.0±4.4yr), a 50 mg/ml liquid. The prescribed 6-MP dose (25-115mg/m2) was given after a fast. 6-MP was quantitated from blood samples (n=13 over 8 hr) by LC-MS/MS. PK analysis was non-compartmental and TPMT genotype was determined by TaqMan PCR. PK parameters were compared using a paired (within group) and unpaired (between group) t test.
RESULTS: There were no TPMT PMs (20EMs, 2 IMs). PK data (mean±SD) are summarized:

AUCN, CMaxN, and Tmax for the 5 vs. 50 mg/ml liquid groups were different. Parameters within each group (i.e. tablet vs. liquid) revealed significant differences in these parameters only in the 5 mg/ml liquid cohort.
CONCLUSION: PK of 6-MP liquid formulations (particularly absorption) appears dependent on drug concentration and perhaps, composition. These differences could impact 6-MP dose selection in children with ALL.