Pharmacokinetics of Lenalidomide in Subjects With Various Degrees of Renal Impairment and in Subjects on Hemodialysis
Version of Record online: 7 MAR 2013
2007 American College of Clinical Pharmacology
The Journal of Clinical Pharmacology
Volume 47, Issue 12, pages 1466–1475, December 2007
How to Cite
Chen, N., Lau, H., Kong, L., Kumar, G., Zeldis, J. B., Knight, R. and Laskin, O. L. (2007), Pharmacokinetics of Lenalidomide in Subjects With Various Degrees of Renal Impairment and in Subjects on Hemodialysis. Journal of Clinical Pharma, 47: 1466–1475. doi: 10.1177/0091270007309563
- Issue online: 7 MAR 2013
- Version of Record online: 7 MAR 2013
- Submitted for publication June 27, 2007; revised version accepted September 1, 2007.
- renal impairment;
The present study investigated the effect of renal impairment and hemodialysis on the pharmacokinetics of lenalidomide following a single 25-mg oral dose in 30 subjects aged 39 to 76 years. A single 25-mg dose was well tolerated by renally impaired subjects. Renal impairment did not alter the oral absorption, protein binding, or nonrenal elimination of lenalidomide. Mean urinary recovery of unchanged lenalidomide was 84% of the dose in subjects with normal renal function (creatinine clearance [CLCr] > 80 mL/min), and it declined to 69%, 38%, and 43% in subjects with mild (50 ≤ CLCr ≤ 80 mL/min), moderate (30 ≤ CLCr < 50 mL/min), and severe (CLCr < 30 mL/min) renal impairment, respectively. The differences in pharmacokinetic parameters between normal renal function and mild renal impairment were minor to modest (11%–32%). As renal impairment progressed to moderate, severe, or end-stage renal disease, total and renal lenalidomide clearance decreased drastically, area under the concentration-time curve increased by approximately 185% to 420%, and t1/2 was prolonged by approximately 6 to 12 hours. A 4-hour hemodialysis removed 31% of lenalidomide in the body. Therefore, lenalidomide dose adjustments should be considered for patients with CLCr < 50 mL/min, and the recommendations are given for the starting doses.