Single-dose pharmacokinetics of lenalidomide in healthy volunteers: Dose proportionality, food effect, and racial sensitivity

Cancer Chemotherapy and Pharmacology

Volumn 70, Issue 5, 2012, Pages 717-725

  Chen, N ^a   Kasserra, C ^a   Reyes, J ^a   Liu, L ^a   Lau, H ^a,b  

^a CELGENE CORPORATION   (United States)

^b Watson Pharmaceuticals Inc   (United States)

Author keywords

Dose proportionality; Food effect; Japanese subjects; Lenalidomide; Pharmacokinetics

Indexed keywords

LENALIDOMIDE; PLACEBO;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CAUCASIAN; CONTROLLED STUDY; CROSSOVER PROCEDURE; DISTRIBUTION VOLUME; DOSE PROPORTIONALITY; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG ELIMINATION; DRUG EXCRETION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ETHNIC OR RACIAL ASPECTS; FEMALE; FOOD; FOOD DRUG INTERACTION; HUMAN; HUMAN EXPERIMENT; JAPANESE; LIPID DIET; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHARMACOLOGICAL PARAMETERS; PRIORITY JOURNAL; PRURITUS; RACIAL SENSITIVITY; RANDOMIZED CONTROLLED TRIAL; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; UPPER RESPIRATORY TRACT INFECTION;

ADMINISTRATION, ORAL; ADULT; ANTINEOPLASTIC AGENTS; AREA UNDER CURVE; ASIAN CONTINENTAL ANCESTRY GROUP; BIOLOGICAL AVAILABILITY; CROSS-OVER STUDIES; DIETARY FATS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; EUROPEAN CONTINENTAL ANCESTRY GROUP; FOOD-DRUG INTERACTIONS; HALF-LIFE; HUMANS; JAPAN; MALE; STEREOISOMERISM; THALIDOMIDE; TIME FACTORS; YOUNG ADULT;

EID: 84871246021     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-012-1966-z     Document Type: Article

References (32)

1. Verhelle D, Corral LG, Wong K, Mueller JH, Moutouh-de Parseval L, Jensen-Pergakes K, Schafer PH, Chen R, Glezer E, Ferguson GD, Lopez-Girona A, Muller GW, Brady HA, Chan KW (2007) Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34 progenitor cells. Cancer Res 67:746-755
2. Escoubet-Lozach L, Lin IL, Jensen-Pergakes K, Brady HA, Gandhi AK, Schafer PH, Muller GW, Worland PJ, Chan KW, Verhelle D (2009) Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res 69:7347-7356
3. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, Munshi NC, Treon SP, Anderson KC (2002) Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 99:4525-4530
4. Dredge K, Horsfall R, Robinson SP, Zhang LH, Lu L, Tang Y, Shirley MA, Muller G, Schafer P, Stirling D, Dalgleish AG, Bartlett JB (2005) Orally administered lenalidomide (CC-5013) is anti-Angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res 69:56-63
5. Chang DH, Liu N, Klimek V, Hassoun H, Mazumder A, Nimer SD, Jagannath S, Dhodapkar MV (2006) Enhancement of liganddependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood 108:618-621
6. Wu L, Adams M, Carter T, Chen R, Muller G, Stirling D, Schafer P, Bartlett JB (2008) Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-Treated CD20 tumor cells. Clin Cancer Res 14:4650-4657
7. Baz R, Walker E, Karam MA, Choueiri TK, Jawde RA, Bruening K, Reed J, Faiman B, Ellis Y, Brand C, Srkalovic G, Andresen S, Knight R, Zeldis J, Hussein MA (2006) Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann Oncol 17:1766-1771
8. Noonan K, Rudraraju L, Ferguson A, Emerling A, Pasetti MF, Huff CA, Borrello I (2012) Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. Clin Cancer Res 18:1426-1434
9. Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, Patterson RT, Stirling DI, Kaplan G (1999) Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-Alpha. J Immunol 163:380-386
10. Zeldis JB, Knight RD, Jacques C, Tozer A, Bizzari JP (2010) Lenalidomide in multiple myeloma: current role and future directions. Expert Opin Pharmacother 11:829-842
11. Revlimid (lenalidomide) prescribing information (last revised May 2012). Celgene Corporation, Summit, NJ, USA. http://www. revlimid.com/docs/Revlimid- Full-PI.pdf. Accessed 4 July 2012
12. Revlimid (lenalidomide) summary of product characteristics (date of first authorization June 2007). Celgene Europe Limited, Uxbridge, UK. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/ human/000717/WC500056018.pdf. Accessed 4 July 2012
13. Revlimid (lenalidomide). http://www.swissmedic.ch/. Accessed date June 4, 2012
14. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, Powell B, Greenberg P, Thomas D, Stone R, Reeder C, Wride K, Patin J, Schmidt M, Zeldis J, Knight R, Myelodysplastic Syndrome-003 Study Investigators (2006) Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355:1456-1465
15. Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, Muus P, Te Boekhorst P, Sanz G, Del Canizo C, Guerci-Bresler A, Nilsson L, Platzbecker U, LubbertM, Quesnel B, CazzolaM,GanserA,Bowen D, Schlegelberger B, AulC,Knight R, Francis J, Fu T, Hellstrom-Lindberg E, MDS-004 Lenalidomide del5q Study Group (2011) A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients withLow-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood 118:3765-3776
16. Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foá R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD, Multiple Myeloma (010) Study Investigators (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357:2123-2132
17. Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD, Multiple Myeloma (009) Study Investigators (2007) Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357:2133-2142
18. Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM (2009) Long-Term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 23:2147-2152
19. Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL, IFM Investigators (2012) Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1782-1791
20. PalumboA,Hajek R, Delforge M, Kropff M, PetrucciMT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA, MM-015 Investigators (2012) Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 366:1759-1769
21. McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C (2012) Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1770-1781
22. Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR, Eastern Cooperative Oncology Group (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11:29-37
23. Ferrajoli A, Lee BN, Schlette EJ, O'Brien SM, Gao H, Wen S, Wierda WG, Estrov Z, Faderl S, Cohen EN, Li C, Reuben JM, Keating MJ (2008) Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood 111:5291-5297
24. Blum W, Klisovic RB, Becker H, Yang X, Rozewski DM, Phelps MA, Garzon R, Walker A, Chandler JC, Whitman SP, Curfman J, Liu S, Schaaf L, Mickle J, Kefauver C, Devine SM, Grever MR, Marcucci G, Byrd JC (2010) Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J Clin Oncol 28:4919-4925
25. Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM (2008) Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 26:4952-4957
26. Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Vose JM (2009) Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's lymphoma. J Clin Oncol 27:5404-5409
27. Chen N, Lau H, Kong L, Kumar G, Zeldis JB, Knight R, Laskin OL (2007) Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis. J Clin Pharmacol 47:1466-1475
28. Chen N, Lau H, Choudhury S, Wang X, Assaf M, Laskin OL (2010) Distribution of lenalidomide into semen of healthy men after multiple oral doses. J Clin Pharmacol 50:767-774
29. Iida S, Chou T, Okamoto S, Nagai H, Hatake K, Murakami H, Takagi T, Shimizu K, Lau H, Takeshita K, Takatoku M, Hotta T (2010) Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol 92:118-126
30. Dahut WL, Aragon-Ching JB, Woo S, Tohnya TM, Gulley JL, Arlen PM, Wright JJ, Ventiz J, Figg WD (2009) Phase I study of oral lenalidomide in patients with refractory metastatic cancer. J Clin Pharmacol 49:650-660
31. Fleisher D, Li C, Zhou Y, Pao LH, Karim A (1999) Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications. Clin Pharmacokinet 36:233-254
32. Chen N, Wen L, Lau H, Surapaneni S, Kumar G (2012) Pharmacokinetics, metabolism and excretion of [(14)C]-lenalidomide following oral administration in healthy male subjects. Cancer Chemother Pharmacol 69:789-797