Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

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

Shida, Seiji MD*; Takahashi, Naoto MD, PhD*; Miura, Masatomo PhD; Niioka, Takenori PhD; Matsumoto, Morio MD, PhD; Hagihara, Masao MD, PhD§; Kobayashi, Takahiro MD*; Abumiya, Maiko MS; Kameoka, Yoshihiro MD, PhD*; Fujishima, Naohito MD, PhD; Tagawa, Hiroyuki MD, PhD*; Hirokawa, Makoto MD, PhD; Sawada, Kenichi MD, PhD*

doi: 10.1097/FTD.0000000000000034
Original Article

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 AUC0–24 predicted from a single lenalidomide plasma concentration measured 8 hours after the administration (C8h) showed the highest correlation with the measured AUC0–24 of lenalidomide (AUC0–24 = 13.0 × C8h + 1305.0; r2 = 0.832). To enhance the correlation between the predicted and the actual AUC0–24 of lenalidomide, we included information regarding lenalidomide elimination by entering creatinine clearance (CCr) data in the predictive formula of lenalidomide AUC0–24. Predicting the AUC0–24 of lenalidomide using data from 2 time points, C0h and C4h, along with CCr data further strengthened the correlation with the measured AUC0–24 of lenalidomide [AUC0–24 = 37.1 × C0h + 6.4 × C4h − 32.1 × CCr + 3265.6; r2 = 0.842].

Conclusions: The AUC0–24 of lenalidomide can be predicted using plasma concentrations measured at only 2 time points, C0h and C4h, 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.

Supplemental Digital Content is Available in the Text.

*Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine;

Department of Pharmacy, Akita University Hospital, Akita, Japan;

Department of Hematology, Nishi-Gunma Hospital, Shibukawa, Japan;

§Department of Hematology, Eiju General Hospital, Tokyo, Japan;

Division of Blood Transfusion and

Clinical Oncology Center, Akita University Hospital, Akita, Japan.

Correspondence: Naoto Takahashi, MD, PhD, Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan (e-mail:

Supported by a grant (No. 24926001) from the Japan Society for the Promotion of Science, Tokyo, Japan.

The authors declare no conflict of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received June 29, 2013

Accepted November 20, 2013

© 2014 by Lippincott Williams & Wilkins