title: A limited sampling model to estimate exposure to lenalidomide in multiple myeloma patients.
abstract: 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; r = 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; r = 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.
authors.affiliation: *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.
authors.forename: Seiji
authors.initials: S
authors.lastname: Shida
authors.forename: Naoto
authors.initials: N
authors.lastname: Takahashi
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Masao
authors.initials: M
authors.lastname: Hagihara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Maiko
authors.initials: M
authors.lastname: Abumiya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kameoka
authors.forename: Naohito
authors.initials: N
authors.lastname: Fujishima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tagawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirokawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sawada
mesh_terms: D020533:Angiogenesis Inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D044466:Asian People; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide