Pharmacokinetics of two 6-mercaptopurine liquid formulations in children with acute lymphoblastic leukemia

Background A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. Methods Twenty-two children (6–17 years) participated in a randomized two-way, crossover study of two cohorts. Group 1 (n = 11; five males) received a 5 mg/ml liquid formulation and the marketed 50 mg 6-MP tablet on separate occasions, and Group 2 (n = 11; five males) received a 50 mg/ml liquid formulation and the marketed tablet. The usual prescribed 6-MP dose (25–115 mg/m2) was given after an 8-hr fast. Serial blood samples were collected over 8 hr postdose. Plasma 6-MP concentrations were determined using a good laboratory practice (GLP)-validated liquid chromatography–tandem mass spectrometry method. PK parameters were calculated using noncompartmental analysis and compared within and between cohorts, and thiopurine methyltransferase (TPMT) genotype was analyzed. Results No patient had a TPMT genotype reflective of a poor metabolizer phenotype. Comparison of PK parameters between 5 and 50 mg/ml treatments revealed significant differences (P