Online citations, reference lists, and bibliographies.

Population Pharmacokinetics Of Pomalidomide

Yan Li, Yejun Xu, Liangang Liu, Xiao-Min Wang, Maria Palmisano, Simon Zhou
Published 2015 · Medicine
Cite This
Download PDF
Analyze on Scholarcy
Share
A population pharmacokinetic (PPK) model of pomalidomide was developed and the influence of demographic and disease-related covariates on PPK parameters was assessed based on data from 6 clinical trials of pomalidomide (dose range, 0.5–10 mg) in healthy participants (n = 96) and patients with multiple myeloma (MM; n = 144). PPK data described herein suggest that systemic clearance of pomalidomide is comparable between healthy study participants and patients with MM. However, apparent peripheral volume of distribution and apparent intercompartmental clearance between central and peripheral compartments were 8- and 3.7-fold higher in patients with MM vs. healthy subjects, suggesting drug exposure is higher in peripheral compartments of patients with MM vs. healthy subjects. Covariate analysis suggested pomalidomide clearance is not affected by demographic factors except for gender, and it is unlikely this factor is clinically relevant. In addition, renal function as measured by creatinine clearance or renal impairment (RI) does not significantly affect clearance of pomalidomide. In conclusion, pomalidomide has robust pharmacokinetic exposure, not affected by demographic factors or renal impairment. Pomalidomide is preferentially taken up by tumors over healthy tissues in patients with MM.
This paper references
Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha.
Laura G. Corral (1999)
10.1111/j.1365-2141.2004.05286.x
Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application.
Toshiaki Hayashi (2005)
Pomalidomide plus lowdose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial
J San Miguel (2013)
10.1182/blood.V96.9.2943
Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.
Teru Hideshima (2000)
10.1016/S1470-2045(13)70380-2
Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial.
Jesús F. San Miguel (2013)
Imnovid (pomalidomide) [summary of product characteristics]. Uxbridge, UK: Celgene Europe
(2013)
10.1016/j.mvr.2008.08.003
The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions.
Ling Lu (2009)
10.1159/000180580
Prediction of creatinine clearance from serum creatinine.
Donald W. Cockcroft (1975)
10.1158/0008-5472.CAN-06-2317
Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells.
Dominique Verhelle (2007)
10.1007/s00280-012-2040-6
Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration
Matthew C. Hoffmann (2012)
and Drug Administration
US Foo (2010)
10.1159/000180580
Prediction of creatinine clearance from serum creatinine.
Cockcroft Dw (1976)
10.1182/blood.V99.12.4525
Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications.
Nicholas Mitsiades (2002)
10.1200/JCO.2004.10.052
Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma.
Steve A. Schey (2004)
andDrugAdministration
US Foo (2013)
10.1016/j.leukres.2014.06.015
Phase II study of pomalidomide in combination with prednisone in patients with myelofibrosis and significant anemia.
Naval Daver (2014)
Supporting Information Additional supporting information may be found in the online version of this article at the publisher's web-site
10.1038/sj.leu.2402295
Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications
D Gupta (2001)
10.1200/JCO.2013.31.15_SUPPL.8585
MM-008 trial: Pharmacokinetics (PK) and tolerability of pomalidomide plus low-dose dexamethasone (POM plus LoDEX) in relapsed/refractory multiple myeloma (RRMM) patients with renal impairment (RI).
Jeffrey V. Matous (2013)
10.1046/j.1365-2710.1999.00246.x
Gender-related differences in pharmacokinetics and their clinical significance.
Einosuke Tanaka (1999)
Pomalyst (pomalidomide) [package insert]. Summit, NJ: Celgene Corporation
(2014)
Guidance for Industry. Pharmacokinetics in patients with impaired renal function-study design, data analysis, and impact on dosing and labeling
(2010)
10.1182/BLOOD.V122.21.5393.5393
MM-008: A Phase 1 Trial Evaluating Pharmacokinetics and Tolerability Of Pomalidomide + Low-Dose Dexamethasone In Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment
Jeffrey V. Matous (2013)
10.1007/s00262-008-0512-7
Immunomodulatory drugs Revlimid® (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation
Dan Zhu (2008)
10.1111/J.1365-2141.2007.06841.X
Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo.
N. Varsha Monica Reddy (2008)
10.1182/blood-2013-11-538835
Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study.
Paul G Richardson (2014)
10.3109/00365528209181087
Age- and sex-related behaviour of gastric acid secretion at the population level.
Matti Kekki (1982)
US Food and Drug Administration. POMALYST 1 (pomalidomide) [prescribing information
(2013)
Guidance for Industry Pharmacokinetics in patients with impaired renal function—study design, data analysis, and impact on dosing and labeling
Us Food (2010)
10.1002/chir.10221
Chiral inversion of the second generation IMiD CC-4047 (ACTIMID ) in human plasma and phosphate-buffered saline.
Steve K. Teo (2003)



This paper is referenced by
10.1038/srep16991
Identification of Synergistic, Clinically Achievable, Combination Therapies for Osteosarcoma
Diana Yu (2015)
10.1002/jcph.1506
Population Pharmacokinetic Model to Assess the Impact of Disease State on Thalidomide Pharmacokinetics.
Allison Gaudy (2019)
10.1002/cpdd.372
Population Pharmacokinetics of Lenalidomide in Healthy Volunteers and Patients With Hematologic Malignancies.
Jamie N. Connarn (2018)
10.1007/s12325-018-0815-9
Pharmacokinetics and Exposure–Response Analyses of Daratumumab in Combination Therapy Regimens for Patients with Multiple Myeloma
Xu Steven Xu (2018)
10.2147/CPAA.S171735
A Phase I, open-label, randomized, crossover study in healthy subjects to evaluate the bioavailability of, and the food effect on, a pomalidomide oral liquid suspension
Yan Li (2018)
10.1002/hon.2485
Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma.
Camille Morival (2017)
10.3390/molecules25020367
Immunomodulatory Drugs Alter the Metabolism and the Extracellular Release of Soluble Mediators by Normal Monocytes
Ida Marie Rundgren (2020)
Biological markers and treatment as prognostic factors in multiple myeloma
Katarina Uttervall (2015)
10.1038/leu.2017.156
Spotlight on pomalidomide: could less be more?
Thomas Zander (2017)
10.1053/j.ajkd.2016.10.026
Pharmacokinetics of Pomalidomide in a Patient Receiving Hemodialysis Using a High-Cutoff Filter.
Kim Dao (2017)
10.1002/bio.3748
A simple and rapid spectrofluorometric determination of pomalidomide in spiked plasma and urine. Application to degradation studies.
Zeynep Aydoğmuş (2019)
10.1016/S2352-3026(19)30249-2
MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1-2a trial.
Marc S Raab (2020)
10.1002/hon.2290
Safety and tolerability of pomalidomide‐based regimens (pomalidomide‐carfilzomib‐dexamethasone with or without cyclophosphamide) in relapsed/refractory multiple myeloma and severe renal dysfunction: a case series
Joshua R. Richter (2017)
10.1002/cpdd.470
An Open‐Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics
Yan Li (2019)
10.1002/jcph.1602
Population Pharmacokinetics and Exposure Response Analysis of Pomalidomide in Subjects With Relapsed or Refractory Multiple Myeloma From the Novel Combination Treatment of Pomalidomide, Bortezomib, and Low-Dose Dexamethasone.
Yan Li (2020)
10.2147/CPAA.S144606
Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function
Yan Li (2017)
10.1158/0008-5472.CAN-17-0502
An Ex Vivo Platform for the Prediction of Clinical Response in Multiple Myeloma.
Ariosto Siqueira Silva (2017)
10.1002/chir.22563
Chiral Separation of Uncharged Pomalidomide Enantiomers Using Carboxymethyl-β-Cyclodextrin: A Validated Capillary Electrophoretic Method.
Zoltán-István Szabó (2016)
10.1002/jssc.201600354
Liquid chromatography with mass spectrometry enantioseparation of pomalidomide on cyclodextrin-bonded chiral stationary phases and the elucidation of the chiral recognition mechanisms by NMR spectroscopy and molecular modeling.
Zoltán-István Szabó (2016)
Semantic Scholar Logo Some data provided by SemanticScholar