Single-dose pharmacokinetics of lenalidomide in healthy volunteers: dose proportionality, food effect, and racial sensitivity

Cancer Chemother Pharmacol. 2012 Nov;70(5):717-25. doi: 10.1007/s00280-012-1966-z. Epub 2012 Sep 6.


Purpose: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Asian People
  • Biological Availability
  • Cross-Over Studies
  • Dietary Fats / administration & dosage
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Food-Drug Interactions*
  • Half-Life
  • Humans
  • Japan
  • Lenalidomide
  • Male
  • Stereoisomerism
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives*
  • Thalidomide / pharmacokinetics
  • Time Factors
  • White People
  • Young Adult


  • Antineoplastic Agents
  • Dietary Fats
  • Thalidomide
  • Lenalidomide