A Limited Sampling Model to Estimate Exposure to Lenalidomide in Multiple Myeloma Patients

Background: The aim of this study was to develop a model able to predict the area under the lenalidomide plasma concentration-time curve (AUC) in multiple myeloma (MM) patients using a limited sampling strategy. Methods: Forty-six hospitalized Japanese MM patients (25 men and 21 women) participated in this study. On days 3-10 of lenalidomide therapy, whole-blood samples were collected just before oral lenalidomide administration, and 1, 2, 4, 8, 12, and 24 hours thereafter. Plasma concentrations of lenalidomide were analyzed using liquid chromatography-tandem mass spectrometry. Results: The AUC(0) (24) predicted from a single lenalidomide plasma concentration measured 8 hours after the administration (C-8h) showed the highest correlation with the measured AUC(0) (24) of lenalidomide (AUC(0) (24) = 13.0 x C-8h + 1305.0; r(2) = 0.832). To enhance the correlation between the predicted and the actual AUC(0) (24) of lenalidomide, we included information regarding lenalidomide elimination by entering creatinine clearance (CCr) data in the predictive formula of lenalidomide AUC(0) (24). Predicting the AUC(0) (24) of lenalidomide using data from 2 time points, C-0h and C-4h, along with CCr data further strengthened the correlation with the measured AUC(0) (24) of lenalidomide [AUC(0) (24) = 37.1 x C-0h + 6.4 x C-4h - 32.1 x CCr + 3265.6; r(2) = 0.842]. Conclusions: The AUC(0) (24) of lenalidomide can be predicted using plasma concentrations measured at only 2 time points, C-0h and C-4h, in combination with CCr. Our study also suggests that the limited sampling strategy approach might help to identify patients with renal function impairment and who, despite dose adjustments, accumulate the drug, leading to a high AUC.