Department of Clinical Pharmacology, Translational Development, Celgene Corporation, Summit, NJ, USA.
Cancer Chemother Pharmacol. 2012 Nov;70(5):717-25. doi: 10.1007/s00280-012-1966-z. Epub 2012 Sep 6.
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.
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.
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.
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.
来那度胺是一种免疫调节药物，在各种血液系统恶性肿瘤中均具有疗效。本研究旨在评估来那度胺的单剂量药代动力学，包括剂量比例性、食物效应和种族敏感性。
共进行了三项研究，包括总共 58 名健康受试者：一项随机、单盲、交替组、单递增剂量研究；一项随机、两向交叉食物效应研究；以及一项随机、双盲、两处理组、自身交叉、单递增剂量研究。
来那度胺口服吸收迅速，给药后约 1 小时达到最大血浆浓度（C（max））。与高脂肪餐同时给药使 AUC 和 C（max）分别减少约 20%和 50%，并使 C（max）达峰时间（t（max））延迟 1.63 小时。然而，III 期试验不考虑食物进行给药；因此，食物效应的临床相关性很小。在 50mg 以下剂量时，末端消除半衰期（t（½））为 3-4 小时，不受食物影响。AUC 和 C（max）与来那度胺单剂量（5-400mg）呈比例关系，总清除率和肾清除率与剂量无关。血浆中 R-到 S-来那度胺的比例随时间保持稳定，约占总药物的 45-55%。日本和白种人受试者之间在药代动力学参数、剂量-暴露关系或对映体比率方面无差异。
在健康受试者中，来那度胺的剂量在 5-400mg 范围内呈现线性药代动力学。尽管食物降低了生物利用度，但这在临床上并不认为是相关的。来那度胺在两个种族群体中均具有良好的耐受性。
