PURPOSE: CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin 
which has recently been FDA approved for treatment of acute myeloid leukemia 
(AML). The current study investigated the pharmacokinetics (PK) of this 
liposomal formulation.
METHODS: CPX-351 PK data (cytarabine, daunorubicin, and metabolites) from a 
phase I study of relapsed and refractory AML were used for the analysis. Therapy 
was given days 1, 3, and 5 of induction (3-134 units/m2). We developed a 
population PK model to characterize CPX-351 disposition.
RESULTS: 39 patients (3589 samples) were evaluated. Liposomal cytarabine and 
daunorubicin were modeled separately with their respective metabolites. A 
one-compartment model fit the parent compounds well; the metabolites required 
two-compartment models. Weight was an independent predictor of liposomal 
volumes; mild renal and liver dysfunction were not predictors of clearance or 
volume (maximum creatinine 1.6 mg/dL and total bilirubin 1.8 mg/dL). Liposomal 
clearances of the two drugs were highly correlated and 1000-fold smaller than 
published non-encapsulated values supporting prolonged encapsulation in the 
liposome.
CONCLUSIONS: The PK model demonstrates prolonged exposure to cytarabine and 
daunorubicin without increases in non-hematologic toxicity that indicates 
retention of the drugs within the liposome. The unique pharmacology of this 
formulation may allow for simplified regimens and improved outcomes.