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An Open‐Label, Phase 1 Study To Assess The Effects Of Hepatic Impairment On Pomalidomide Pharmacokinetics

Y. Li, X. Wang, L. Liu, Chengyue Zhang, D. Gómez, J. Reyes, M. Palmisano, S. Zhou
Published 2019 · Medicine

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Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1‐21 of repeated 28‐day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open‐label, single‐dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4‐mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (Cmax) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4‐mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child‐Pugh classes A or B), a 3‐mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child‐Pugh class C), a 2‐mg starting daily dose (50% dose reduction).
This paper references
in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling
FDA. Pharmacokinetic (2018)
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)
10.1182/BLOOD.V99.12.4525
Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications.
N. Mitsiades (2002)
10.1016/j.leukres.2014.06.015
Phase II study of pomalidomide in combination with prednisone in patients with myelofibrosis and significant anemia.
N. Daver (2014)
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)
10.1182/BLOOD.V96.9.2943
Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.
T. Hideshima (2000)
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.
L. Lu (2009)
Pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling. FDA Guidance
Pharmacokinetics in patients with impaired hepatic function : study design , data analysis , and impact on dosing and labeling
C Kasserra (2003)
10.1002/jcph.455
Population Pharmacokinetics of Pomalidomide
Y. Li (2015)
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)
Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha.
L. Corral (1999)
10.1053/j.ajkd.2016.10.026
Pharmacokinetics of Pomalidomide in a Patient Receiving Hemodialysis Using a High-Cutoff Filter.
Kim Dao (2017)
10.1111/j.1365-2141.2004.05286.x
Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application
T. Hayashi (2005)
COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE ( CHMP ) GUIDELINE ON THE EVALUATION OF THE PHARMACOKINETICS OF MEDICINAL PRODUCTS IN PATIENTS WITH IMPAIRED HEPATIC FUNCTION
(2005)
10.1002/jcph.384
Pomalidomide: Evaluation of cytochrome P450 and transporter‐mediated drug–drug interaction potential in vitro and in healthy subjects
C. Kasserra (2015)
10.1007/s00280-012-2040-6
Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration
M. Hoffmann (2012)
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.
P. Richardson (2014)
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.
J. Miguel (2013)
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)
10.1124/jpet.114.215251
Modeling and Simulation to Probe the Pharmacokinetic Disposition of Pomalidomide R- and S-Enantiomers
Y. Li (2014)
10.1517/17425255.2013.827169
Pharmacokinetic evaluation of pomalidomide for the treatment of myeloma
Francesca Gay (2013)
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. Reddy (2008)
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)



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