title: Single-dose pharmacokinetics of lenalidomide in healthy volunteers: dose proportionality, food effect, and racial sensitivity.
abstract: OBJECTIVE
  Lenalidomide is an immunomodulatory drug with efficacy in various hematological malignancies. The purpose of these studies was to evaluate the single-dose pharmacokinetics of lenalidomide, including dose proportionality, food effect, and racial sensitivity.
  
  
  METHODS
  Three studies were conducted including a total of 58 healthy subjects: a randomized, single-blind, alternating group, single-ascending dose study; a randomized, two-way crossover food effect study; and a randomized, double-blind, two-group, within-subject, single-ascending dose study.
  
  
  RESULTS
  Oral absorption of lenalidomide was rapid and the maximum plasma concentration (C                   (max)) was observed approximately 1 h post-dose. Co-administration with a high-fat meal reduced the area under the concentration-time curve (AUC) and C                   (max) by approximately 20 and 50 %, respectively, and delayed time to C                   (max) (t                   (max)) by 1.63 h. However, phase III trials were dosed without regard to food; therefore, clinical relevance of the food effect was minimal. The terminal elimination half-life (t                   (½)) was 3-4 h at doses up to 50 mg and was not affected by food. The AUC and C                   (max) were proportional to lenalidomide single doses (5-400 mg), and total and renal clearance were dose-independent. The R- to S-lenalidomide ratio in plasma was stable over time, approximately 45-55 % of total drug. There were no differences in pharmacokinetic parameters, dose-exposure relationship, or enantiomeric ratio, between Japanese and Caucasian subjects.
  
  
  CONCLUSIONS
  Lenalidomide displayed linear pharmacokinetics from doses 5-400 mg in healthy subjects. Although food reduced bioavailability, this was not considered clinically relevant. Lenalidomide was generally well tolerated in both ethnic groups.
authors.affiliation: Department of Clinical Pharmacology, Translational Development, Celgene Corporation, Summit, NJ, USA. nchen@celgene.com
authors.forename: N
authors.initials: N
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Kasserra
authors.forename: J
authors.initials: J
authors.lastname: Reyes
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Lau
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D007564:Japan; D000077269:Lenalidomide; D008297:Male; D013237:Stereoisomerism; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013997:Time Factors; D044465:White People; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D004041:Dietary Fats; D013792:Thalidomide; D000077269:Lenalidomide