Hughes, Jim H, Phelps, Mitch A, Upton, Richard N, Reuter Lange, Stephanie E, Gao, Yue, Byrd, John C, Grever, Michael R, Hofmeister, Craig C, Marcucci, Guido, Blum, William, Blum, Kristie A, Foster, David JR
Aims: Lenalidomide is an immunomodulatory imide drug used broadly in the treatment of multiple myeloma and lymphoma. It continues to be evaluated in chroniclymphocytic leukaemia (CLL) at lower doses due to dose‐related toxicities including tumour flare and tumour lysis syndrome. This study aimed to develop a population pharmacokinetic model for lenalidomide in multiple cancers, including CLL, to identify any disease‐related differences in disposition. Methods: Lenalidomide concentrations from 4 clinical trials were collated (1999 samples, 125 subjects), covering 4 cancers (multiple myeloma, CLL, acute myeloid leukaemia and acute lymphoblastic leukaemia) and a large dose range (2.5–75 mg).A population pharmacokinetic model was developed with NONMEM and patient demographics were tested as covariates. Results: The data were best fitted by a 1‐compartment kinetic model with absorption described by 7 transit compartments. Clearance and volume of distribution were allometrically scaled for fat‐free mass. The population parameter estimates for apparent clearance, apparent volume of distribution and transit rate constant were 12 L/h(10.8–13.6), 68.8 L (61.8–76.3), and 13.5 h−1 (11.9–36.8) respectively. Patients with impaired renal function (creatinine clearance
