Online citations, reference lists, and bibliographies.

Pomalidomide: Evaluation Of Cytochrome P450 And Transporter-mediated Drug-drug Interaction Potential In Vitro And In Healthy Subjects.

Claudia Kasserra, Mahmoud S. Assaf, Matthew Hoffmann, Yan Li, Liangang Liu, Xiao-Min Wang, Gondi Kumar, Maria Palmisano
Published 2015 · Medicine
Cite This
Download PDF
Analyze on Scholarcy
Share
Pomalidomide offers an alternative for patients with relapsed/refractory multiple myeloma who have exhausted treatment options with lenalidomide and bortezomib. Little is known about pomalidomide's potential for drug-drug interactions (DDIs); as pomalidomide clearance includes hydrolysis and cytochrome P450 (CYP450)-mediated hydroxylation, possible DDIs via CYP450 and drug-transporter proteins were investigated in vitro and in a clinical study. In vitro pomalidomide was neither an inducer nor inhibitor of CYP450, nor an inhibitor of transporter proteins P glycoprotein (P-gp), BCRP, OAT1, OAT3, OCT2, OATP1B1, and OATP1B3. Oxidative metabolism of pomalidomide was predominately mediated by CYP1A2 and CYP3A4, and pomalidomide was shown to be a P-gp substrate. In healthy males, co-administration of oral (4 mg) pomalidomide with ketoconazole (CYP3A/P-gp inhibitor) or carbamazepine (CYP3A/P-gp inducer) did not result in clinically relevant changes in pomalidomide exposure. Co-administration of pomalidomide with fluvoxamine (CYP1A2 inhibitor) in the presence of ketoconazole approximately doubled pomalidomide exposure. Pomalidomide appears to have low potential for clinically relevant DDI and is unlikely to affect the clinical exposure of other drugs. Avoid co-administration of strong CYP1A2 inhibitors unless medically necessary. Pomalidomide dose should be reduced by 50% if co-administered with strong CYP1A2 inhibitors and strong CYP3A/P-gp inhibitors.
This paper references
10.1182/blood.V96.9.2943
Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.
Teru Hideshima (2000)
Absorption, metabolism and excretion of ( 14 C)pomalidomide in humans following oral administration
Matthew HoffmannClaudia (2013)
10.1182/blood-2012-08-450742
Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib.
Paul G Richardson (2013)
10.1111/j.1365-2141.2008.07013.x
Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation.
Matthew J Streetly (2008)
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)
10.1111/j.1365-2125.1992.tb04089.x
Autoinduction and steady-state pharmacokinetics of carbamazepine and its major metabolites.
T B Kudriakova (1992)
10.3109/9781420016840-5
Clinical Pharmacology Review
Doug Humber (2007)
10.1124/dmd.105.007633
GLUCURONIDATION CONVERTS GEMFIBROZIL TO A POTENT, METABOLISM-DEPENDENT INHIBITOR OF CYP2C8: IMPLICATIONS FOR DRUG-DRUG INTERACTIONS
Brian W Ogilvie (2006)
10.1007/s00280-012-2040-6
Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration
Matthew C. Hoffmann (2012)
10.1016/j.pharmthera.2012.12.007
Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation.
Ulrich M. Zanger (2013)
10.1067/mcp.2001.116891
Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential--toward a consensus.
Geoffrey T Tucker (2001)
10.1182/blood.V99.12.4525
Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications.
Nicholas Mitsiades (2002)
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)
10.1124/dmd.32.6.647
Validated assays for human cytochrome P450 activities.
Robert L. Walsky (2004)
10.1002/9783527630905
Metabolism of Drugs and Other Xenobiotics: ANZENBACHER:XENOBIOTICS O-BK
Pavel Anzenbacher (2012)
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)
10.1201/b14003-8
In vitro approaches for studying the inhibition of drug metabolism enzymes and identifying the drug-metabolizing enzymes responsible for the metabolism of drugs
Anup Madan (2002)
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)
An observational multi-cohort study on the use and safety of Combivir scored tablets among HIV-infected children and adolescents. Report to the European Medicines Agency (EMA)/ Committee for Medicinal Products for Human Use (CHMP)
Heather Bailey (2014)
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/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.1365-2125.2009.03457.x
The effect on sotrastaurin pharmacokinetics of strong CYP3A inhibition by ketoconazole.
John M. Kovarik (2009)
10.2165/00003088-197803020-00003
Clinical Pharmacokinetics of Carbamazepine
Leif Bertilsson (1978)
10.1006/abbi.1996.0294
Effects of freezing, thawing, and storing human liver microsomes on cytochrome P450 activity.
Robin Pearce (1996)
Accelerated Communication GLUCURONIDATION CONVERTS GEMFIBROZIL TO A POTENT , METABOLISM-DEPENDENT INHIBITOR OF CYP 2 C 8 : IMPLICATIONS FOR DRUG-DRUG INTERACTIONS
Brian W Ogilvie (2005)
10.2165/00003088-199427030-00002
Clinical Pharmacokinetics of Fluvoxamine
Emilio Perucca (1994)
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)
Cytochrome P450 polymorphism--molecular, metabolic, and pharmacogenetic aspects. II. Participation of CYP isoenzymes in the metabolism of endogenous substances and drugs.
Piotr Tomaszewski (2008)
10.1111/j.1365-2141.2004.05286.x
Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application.
Toshiaki Hayashi (2005)
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)
10.1021/tx4004215
Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide.
Goutam Chowdhury (2014)



This paper is referenced by
10.1002/cpdd.470
An Open‐Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics
Yan Li (2019)
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)
10.1038/onc.2015.245
Immunomodulatory drugs target IKZF1-IRF4-MYC axis in primary effusion lymphoma in a cereblon-dependent manner and display synergistic cytotoxicity with BRD4 inhibitors
Ramakrishnan Gopalakrishnan (2016)
10.1007/s40265-017-0833-y
Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma
Sheridan M. Hoy (2017)
Pomalidomide for multiple
Guillemette Fouquet (2014)
10.1007/s40262-017-0506-8
Renal Drug Transporters and Drug Interactions
Anton Ivanyuk (2017)
10.1002/hon.2485
Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma.
Camille Morival (2017)
10.1002/jcph.1145
In Vivo Assessment of the Effect of CYP1A2 Inhibition and Induction on Pomalidomide Pharmacokinetics in Healthy Subjects
Yan Li (2018)
10.1111/cts.12703
Pivotal Considerations for Optimal Deployment of Healthy Volunteers in Oncology Drug Development
Mariam A Ahmed (2019)
10.1182/bloodadvances.2019031732
Genome-wide CRISPR screens reveal genetic mediators of cereblon modulator toxicity in primary effusion lymphoma.
Ajinkya Patil (2019)
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/j.revmed.2015.04.007
[Pomalidomide for multiple myeloma].
Gerhard Fouquet (2015)
10.1586/17474086.2014.966074
Pomalidomide for multiple myeloma
Guillemette Fouquet (2014)
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)
10.1016/J.REVMED.2015.04.007
Le pomalidomide dans le myélome multiple
Guillemette Fouquet (2015)
10.1002/jcph.1453
Drug‐Drug Interaction Study to Assess the Effect of Cytochrome P450 Inhibition and Induction on the Pharmacokinetics of the Novel Cereblon Modulator Avadomide (CC‐122) in Healthy Adult Subjects
Ken Ogasawara (2019)
10.21320/2500-2139-2015-8-4-379-389
Pomalidomide for Treatment of Relapsed and Refractory Multiple Myeloma
S. V. Semochkin (2015)
10.1080/00498254.2016.1247218
Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice
Makiko Shimizu (2017)
10.7448/IAS.20.1.21534
Alcohol-antiretroviral interactive toxicity beliefs as a potential barrier to HIV pre-exposure prophylaxis among men who have sex with men
Seth C Kalichman (2017)
10.18632/oncotarget.17960
Restoration of immune surface molecules in Kaposi sarcoma-associated herpesvirus infected cells by lenalidomide and pomalidomide.
David A. Davis (2017)
10.1007/s00280-015-2912-7
A Phase 1, double-blind, 4-period crossover study to investigate the effects of pomalidomide on QT interval in healthy male subjects
Sabiha A. Mondal (2015)
Etude de l'impact clinique et immunologique d'un traitement par lénalidomide dans la maladie de Kaposi liée au VIH
Aude Desnoyer (2015)
10.1007/s40265-014-0196-6
Pomalidomide: A Review of Its Use in Patients with Recurrent Multiple Myeloma
Lesley J. Scott (2014)
Semantic Scholar Logo Some data provided by SemanticScholar