Purpose: Lenalidomide disease-specific toxicity profiles and potentially life-threatening adverse events support the consideration of diversity in starting doses. The aim of this study was to conduct a population pharmacokinetic analysis of lenalidomide in multiple myeloma patients to identify and evaluate non-studied covariates that could be used for dose individualization.
Methods: Blood samples were collected from 15 multiple myeloma patients. Nonlinear mixed-effects modeling was used to develop a population pharmacokinetic model and perform covariate analysis. The developed model was used to simulate dose schedules in order to explore the need of different dosing regimens in patients with different covariate values.
Results: The data were accurately described by a one-compartment model with first-order elimination. Absorption was best described using three transit compartments. Creatinine clearance and body surface area were identified as covariates affecting apparent clearance and apparent volume of distribution, respectively. Simulations revealed that lower starting doses than the standard 25 mg/daily could be used in patients with body surface area below 1.8 m2 and even higher doses might be necessary for patients with normal renal function and large body surface area.
Conclusions: This study identified creatinine clearance and body surface area as covariates that have a clinically relevant impact on lenalidomide pharmacokinetics using population pharmacokinetics. In addition, the developed population pharmacokinetic model can be used to individualize lenalidomide dose in multiple myeloma patients, taking into account not only creatinine clearance but also body surface area.
Keywords: Lenalidomide; Multiple myeloma; Personalized medicine; Population pharmacokinetics.