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

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(1/2)) 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.