Eintrag weiter verarbeiten
Population Pharmacokinetics and Exposure Response Analysis of Pomalidomide in Subjects With Relapsed or Refractory Multiple Myeloma From the Novel Combination Treatment of Pomalido...
Gespeichert in:
| Zeitschriftentitel: | The Journal of Clinical Pharmacology |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | The Journal of Clinical Pharmacology, 60, 2020, 8, S. 1061-1075 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Li, Yan Kassir, Nastya Wang, Xiaomin Palmisano, Maria Zhou, Simon Li, Yan Kassir, Nastya Wang, Xiaomin Palmisano, Maria Zhou, Simon |
|---|---|
| author |
Li, Yan Kassir, Nastya Wang, Xiaomin Palmisano, Maria Zhou, Simon |
| spellingShingle |
Li, Yan Kassir, Nastya Wang, Xiaomin Palmisano, Maria Zhou, Simon The Journal of Clinical Pharmacology 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 Pharmacology (medical) Pharmacology |
| author_sort |
li, yan |
| spelling |
Li, Yan Kassir, Nastya Wang, Xiaomin Palmisano, Maria Zhou, Simon 0091-2700 1552-4604 Wiley Pharmacology (medical) Pharmacology http://dx.doi.org/10.1002/jcph.1602 <jats:title>Abstract</jats:title><jats:p>Multiple myeloma is an incurable progressive neoplastic disease that accounts for 10% of all hematologic malignancies. Even though significant progress has been made in the treatment of newly diagnosed multiple myeloma, the disease follows a relapsing course in the majority of patients, and there is a need for more effective therapeutic options for the treatment of relapsed or refractory multiple myeloma. CC‐4047‐MM‐005 and CC‐4047‐MM‐007 were phase 1 and 3 studies to evaluate the novel combination of pomalidomide, bortezomib, and low‐dose dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have already received lenalidomide‐based treatments early. This analysis was performed to characterize the population pharmacokinetics (PK) of pomalidomide from the combination treatment and to examine exposure‐response relationships. Our analysis showed that pomalidomide concentration‐time profiles from the combination treatment were adequately described with a 1‐compartment PK model, with first‐order absorption and elimination and pomalidomide exhibiting linear and time‐invariant PK with moderate variability from the combination treatment. Except for the body surface area, none of the tested covariates had an effect on pomalidomide PK. Although body surface area was identified as a statistically significant covariate of pomalidomide PK, the impact was not deemed clinically relevant. A flat exposure‐response curve was observed, consistent with a near‐saturated drug effect at the tested exposure range suggesting an appropriately recommended clinical dose of 4 mg of pomalidomide for the combination treatment. Finally, pomalidomide exposure was not associated with higher probabilities of dose interruption during cycle 1 or dose reduction during the treatment period.</jats:p> 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 The Journal of Clinical Pharmacology |
| doi_str_mv |
10.1002/jcph.1602 |
| facet_avail |
Online |
| finc_class_facet |
Chemie und Pharmazie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9qY3BoLjE2MDI |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9qY3BoLjE2MDI |
| institution |
DE-Zi4 DE-Gla1 DE-15 DE-Pl11 DE-Rs1 DE-14 DE-105 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-D161 |
| imprint |
Wiley, 2020 |
| imprint_str_mv |
Wiley, 2020 |
| issn |
0091-2700 1552-4604 |
| issn_str_mv |
0091-2700 1552-4604 |
| language |
English |
| mega_collection |
Wiley (CrossRef) |
| match_str |
li2020populationpharmacokineticsandexposureresponseanalysisofpomalidomideinsubjectswithrelapsedorrefractorymultiplemyelomafromthenovelcombinationtreatmentofpomalidomidebortezomibandlowdosedexamethasone |
| publishDateSort |
2020 |
| publisher |
Wiley |
| recordtype |
ai |
| record_format |
ai |
| series |
The Journal of Clinical Pharmacology |
| source_id |
49 |
| title |
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 |
| title_unstemmed |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_short |
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 |
| title_sort |
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 |
| topic |
Pharmacology (medical) Pharmacology |
| url |
http://dx.doi.org/10.1002/jcph.1602 |
| publishDate |
2020 |
| physical |
1061-1075 |
| description |
<jats:title>Abstract</jats:title><jats:p>Multiple myeloma is an incurable progressive neoplastic disease that accounts for 10% of all hematologic malignancies. Even though significant progress has been made in the treatment of newly diagnosed multiple myeloma, the disease follows a relapsing course in the majority of patients, and there is a need for more effective therapeutic options for the treatment of relapsed or refractory multiple myeloma. CC‐4047‐MM‐005 and CC‐4047‐MM‐007 were phase 1 and 3 studies to evaluate the novel combination of pomalidomide, bortezomib, and low‐dose dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have already received lenalidomide‐based treatments early. This analysis was performed to characterize the population pharmacokinetics (PK) of pomalidomide from the combination treatment and to examine exposure‐response relationships. Our analysis showed that pomalidomide concentration‐time profiles from the combination treatment were adequately described with a 1‐compartment PK model, with first‐order absorption and elimination and pomalidomide exhibiting linear and time‐invariant PK with moderate variability from the combination treatment. Except for the body surface area, none of the tested covariates had an effect on pomalidomide PK. Although body surface area was identified as a statistically significant covariate of pomalidomide PK, the impact was not deemed clinically relevant. A flat exposure‐response curve was observed, consistent with a near‐saturated drug effect at the tested exposure range suggesting an appropriately recommended clinical dose of 4 mg of pomalidomide for the combination treatment. Finally, pomalidomide exposure was not associated with higher probabilities of dose interruption during cycle 1 or dose reduction during the treatment period.</jats:p> |
| container_issue |
8 |
| container_start_page |
1061 |
| container_title |
The Journal of Clinical Pharmacology |
| container_volume |
60 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792339538970935302 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T15:49:20.621Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Population+Pharmacokinetics+and+Exposure+Response+Analysis+of+Pomalidomide+in+Subjects+With+Relapsed+or+Refractory+Multiple+Myeloma+From+the+Novel+Combination+Treatment+of+Pomalidomide%2C+Bortezomib%2C+and+Low%E2%80%90Dose+Dexamethasone&rft.date=2020-08-01&genre=article&issn=1552-4604&volume=60&issue=8&spage=1061&epage=1075&pages=1061-1075&jtitle=The+Journal+of+Clinical+Pharmacology&atitle=Population+Pharmacokinetics+and+Exposure+Response+Analysis+of+Pomalidomide+in+Subjects+With+Relapsed+or+Refractory+Multiple+Myeloma+From+the+Novel+Combination+Treatment+of+Pomalidomide%2C+Bortezomib%2C+and+Low%E2%80%90Dose+Dexamethasone&aulast=Zhou&aufirst=Simon&rft_id=info%3Adoi%2F10.1002%2Fjcph.1602&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792339538970935302 |
| author | Li, Yan, Kassir, Nastya, Wang, Xiaomin, Palmisano, Maria, Zhou, Simon |
| author_facet | Li, Yan, Kassir, Nastya, Wang, Xiaomin, Palmisano, Maria, Zhou, Simon, Li, Yan, Kassir, Nastya, Wang, Xiaomin, Palmisano, Maria, Zhou, Simon |
| author_sort | li, yan |
| container_issue | 8 |
| container_start_page | 1061 |
| container_title | The Journal of Clinical Pharmacology |
| container_volume | 60 |
| description | <jats:title>Abstract</jats:title><jats:p>Multiple myeloma is an incurable progressive neoplastic disease that accounts for 10% of all hematologic malignancies. Even though significant progress has been made in the treatment of newly diagnosed multiple myeloma, the disease follows a relapsing course in the majority of patients, and there is a need for more effective therapeutic options for the treatment of relapsed or refractory multiple myeloma. CC‐4047‐MM‐005 and CC‐4047‐MM‐007 were phase 1 and 3 studies to evaluate the novel combination of pomalidomide, bortezomib, and low‐dose dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have already received lenalidomide‐based treatments early. This analysis was performed to characterize the population pharmacokinetics (PK) of pomalidomide from the combination treatment and to examine exposure‐response relationships. Our analysis showed that pomalidomide concentration‐time profiles from the combination treatment were adequately described with a 1‐compartment PK model, with first‐order absorption and elimination and pomalidomide exhibiting linear and time‐invariant PK with moderate variability from the combination treatment. Except for the body surface area, none of the tested covariates had an effect on pomalidomide PK. Although body surface area was identified as a statistically significant covariate of pomalidomide PK, the impact was not deemed clinically relevant. A flat exposure‐response curve was observed, consistent with a near‐saturated drug effect at the tested exposure range suggesting an appropriately recommended clinical dose of 4 mg of pomalidomide for the combination treatment. Finally, pomalidomide exposure was not associated with higher probabilities of dose interruption during cycle 1 or dose reduction during the treatment period.</jats:p> |
| doi_str_mv | 10.1002/jcph.1602 |
| facet_avail | Online |
| finc_class_facet | Chemie und Pharmazie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9qY3BoLjE2MDI |
| imprint | Wiley, 2020 |
| imprint_str_mv | Wiley, 2020 |
| institution | DE-Zi4, DE-Gla1, DE-15, DE-Pl11, DE-Rs1, DE-14, DE-105, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-D161 |
| issn | 0091-2700, 1552-4604 |
| issn_str_mv | 0091-2700, 1552-4604 |
| language | English |
| last_indexed | 2024-03-01T15:49:20.621Z |
| match_str | li2020populationpharmacokineticsandexposureresponseanalysisofpomalidomideinsubjectswithrelapsedorrefractorymultiplemyelomafromthenovelcombinationtreatmentofpomalidomidebortezomibandlowdosedexamethasone |
| mega_collection | Wiley (CrossRef) |
| physical | 1061-1075 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | Wiley |
| record_format | ai |
| recordtype | ai |
| series | The Journal of Clinical Pharmacology |
| source_id | 49 |
| spelling | Li, Yan Kassir, Nastya Wang, Xiaomin Palmisano, Maria Zhou, Simon 0091-2700 1552-4604 Wiley Pharmacology (medical) Pharmacology http://dx.doi.org/10.1002/jcph.1602 <jats:title>Abstract</jats:title><jats:p>Multiple myeloma is an incurable progressive neoplastic disease that accounts for 10% of all hematologic malignancies. Even though significant progress has been made in the treatment of newly diagnosed multiple myeloma, the disease follows a relapsing course in the majority of patients, and there is a need for more effective therapeutic options for the treatment of relapsed or refractory multiple myeloma. CC‐4047‐MM‐005 and CC‐4047‐MM‐007 were phase 1 and 3 studies to evaluate the novel combination of pomalidomide, bortezomib, and low‐dose dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have already received lenalidomide‐based treatments early. This analysis was performed to characterize the population pharmacokinetics (PK) of pomalidomide from the combination treatment and to examine exposure‐response relationships. Our analysis showed that pomalidomide concentration‐time profiles from the combination treatment were adequately described with a 1‐compartment PK model, with first‐order absorption and elimination and pomalidomide exhibiting linear and time‐invariant PK with moderate variability from the combination treatment. Except for the body surface area, none of the tested covariates had an effect on pomalidomide PK. Although body surface area was identified as a statistically significant covariate of pomalidomide PK, the impact was not deemed clinically relevant. A flat exposure‐response curve was observed, consistent with a near‐saturated drug effect at the tested exposure range suggesting an appropriately recommended clinical dose of 4 mg of pomalidomide for the combination treatment. Finally, pomalidomide exposure was not associated with higher probabilities of dose interruption during cycle 1 or dose reduction during the treatment period.</jats:p> 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 The Journal of Clinical Pharmacology |
| spellingShingle | Li, Yan, Kassir, Nastya, Wang, Xiaomin, Palmisano, Maria, Zhou, Simon, The Journal of Clinical Pharmacology, 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, Pharmacology (medical), Pharmacology |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| title_unstemmed | 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 |
| topic | Pharmacology (medical), Pharmacology |
| url | http://dx.doi.org/10.1002/jcph.1602 |