Published in:
01-11-2012 | Original Article
Single-dose pharmacokinetics of lenalidomide in healthy volunteers: dose proportionality, food effect, and racial sensitivity
Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2012
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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.