Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis.
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 [CL(Cr)] > 80 mL/min), and it declined to 69%, 38%, and 43% in subjects with mild (50 < or = CL(Cr) < or = 80 mL/min), moderate (30 < or = CL(Cr) < 50 mL/min), and severe (CL(Cr) < 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 t((1/2)) 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 CL(Cr) < 50 mL/min, and the recommendations are given for the starting doses.
Chen
Nianhang
N
Celgene Corporation, 86 Morris Avenue, Summit, NJ 07091, USA. nchen@celgene.com
Lau
Henry
H
Kong
Linghui
L
Kumar
Gondi
G
Zeldis
Jerome B
JB
Knight
Robert
R
Laskin
Oscar L
OL
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D000077269:Lenalidomide; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006435:Renal Dialysis; D012720:Severity of Illness Index; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide