title: Population pharmacokinetics of lenalidomide in multiple myeloma patients.
abstract: OBJECTIVE
  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 m2and 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.
authors.affiliation: Pharmacy Department, Doctor Peset University Hospital of Valencia, Gaspar Aguilar Avenue, 90, 46017, Valencia, Spain. guglieri_bea@gva.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Guglieri-López
authors.affiliation: Pharmacy Department, University Clinical Hospital of Valencia, Blasco Ibañez Avenue, 17, 46010, Valencia, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pérez-Pitarch
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: Dirk Jan A R
authors.initials: DJ
authors.lastname: Moes
authors.affiliation: Pharmacy Department, Doctor Peset University Hospital of Valencia, Gaspar Aguilar Avenue, 90, 46017, Valencia, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Porta-Oltra
authors.affiliation: Pharmacy Department, Doctor Peset University Hospital of Valencia, Gaspar Aguilar Avenue, 90, 46017, Valencia, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Climente-Martí
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: Henk Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Vicent Andrés Estellés Avenue, 46100, Burjassot, Valencia, Spain.|Molecular Recognition and Technological Development Institute, Centro Mixto Universidad Politécnica de Valencia-Universidad de Valencia, Valencia, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Merino-Sanjuán
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D001830:Body Surface Area; D003404:Creatinine / Q000378:metabolism; D006801:Humans; D000077269:Lenalidomide; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D003404:Creatinine; D000077269:Lenalidomide
keywords: Lenalidomide; Multiple myeloma; Personalized medicine; Population pharmacokinetics