Single-dose pharmacokinetics of lenalidomide in healthy volunteers: dose
proportionality, food effect, and racial sensitivity.
Author(s): Chen N, Kasserra C, Reyes J, Liu L, Lau H.
Affiliation(s): Department of Clinical Pharmacology, Translational Development, Celgene
Corporation, Summit, NJ, USA. nchen@celgene.com
Publication date & source: 2012, Cancer Chemother Pharmacol. , 70(5):717-25
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.
|