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Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma

PURPOSE: The established two-analyte integrated population pharmacokinetic model was applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following bodyweight-based dosing. METHODS: Model si...

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Autores principales: Lu, Dan, Lu, Tong, Shi, Rong, Gibiansky, Leonid, Agarwal, Priya, Shemesh, Colby S., Dere, Randall C., Ogbu, Uzor, Hirata, Jamie, Chanu, Pascal, Girish, Sandhya, Jin, Jin Yan, Li, Chunze, Miles, Dale
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708381/
https://www.ncbi.nlm.nih.gov/pubmed/33258982
http://dx.doi.org/10.1007/s11095-020-02933-6
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author Lu, Dan
Lu, Tong
Shi, Rong
Gibiansky, Leonid
Agarwal, Priya
Shemesh, Colby S.
Dere, Randall C.
Ogbu, Uzor
Hirata, Jamie
Chanu, Pascal
Girish, Sandhya
Jin, Jin Yan
Li, Chunze
Miles, Dale
author_facet Lu, Dan
Lu, Tong
Shi, Rong
Gibiansky, Leonid
Agarwal, Priya
Shemesh, Colby S.
Dere, Randall C.
Ogbu, Uzor
Hirata, Jamie
Chanu, Pascal
Girish, Sandhya
Jin, Jin Yan
Li, Chunze
Miles, Dale
author_sort Lu, Dan
collection PubMed
description PURPOSE: The established two-analyte integrated population pharmacokinetic model was applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following bodyweight-based dosing. METHODS: Model simulations based on individual empirical Bayes estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal functions. Extrinsic factors included rituximab/obinutuzumab or bendamustine combination with pola and manufacturing process. The predicted impact on exposures along with the established exposure-response relationships were used to assess clinical relevance. RESULTS: No clinically meaningful differences in Cycle 6 pola exposures were found for the following subgroups: bodyweight 100–146 kg versus 38–<100 kg, age ≥ 65 years versus <65 years, female versus male, mild hepatic impairment versus normal, mild-to-moderate renal impairment versus normal. Co-administration of rituximab/obinutuzumab or bendamustine, and change in the pola manufacturing process, also had no meaningful impact on PK. CONCLUSIONS: In patients with NHL, bodyweight-based dosing is adequate, and no further dose adjustment is recommended for the heavier subgroup (100–146 kg). In addition, no dose adjustments are recommended for other subgroups based on intrinsic/extrinsic factors evaluated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-020-02933-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-77083812020-12-03 Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma Lu, Dan Lu, Tong Shi, Rong Gibiansky, Leonid Agarwal, Priya Shemesh, Colby S. Dere, Randall C. Ogbu, Uzor Hirata, Jamie Chanu, Pascal Girish, Sandhya Jin, Jin Yan Li, Chunze Miles, Dale Pharm Res Research Paper PURPOSE: The established two-analyte integrated population pharmacokinetic model was applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following bodyweight-based dosing. METHODS: Model simulations based on individual empirical Bayes estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal functions. Extrinsic factors included rituximab/obinutuzumab or bendamustine combination with pola and manufacturing process. The predicted impact on exposures along with the established exposure-response relationships were used to assess clinical relevance. RESULTS: No clinically meaningful differences in Cycle 6 pola exposures were found for the following subgroups: bodyweight 100–146 kg versus 38–<100 kg, age ≥ 65 years versus <65 years, female versus male, mild hepatic impairment versus normal, mild-to-moderate renal impairment versus normal. Co-administration of rituximab/obinutuzumab or bendamustine, and change in the pola manufacturing process, also had no meaningful impact on PK. CONCLUSIONS: In patients with NHL, bodyweight-based dosing is adequate, and no further dose adjustment is recommended for the heavier subgroup (100–146 kg). In addition, no dose adjustments are recommended for other subgroups based on intrinsic/extrinsic factors evaluated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-020-02933-6) contains supplementary material, which is available to authorized users. Springer US 2020-12-01 2020 /pmc/articles/PMC7708381/ /pubmed/33258982 http://dx.doi.org/10.1007/s11095-020-02933-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Paper
Lu, Dan
Lu, Tong
Shi, Rong
Gibiansky, Leonid
Agarwal, Priya
Shemesh, Colby S.
Dere, Randall C.
Ogbu, Uzor
Hirata, Jamie
Chanu, Pascal
Girish, Sandhya
Jin, Jin Yan
Li, Chunze
Miles, Dale
Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma
title Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma
title_full Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma
title_fullStr Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma
title_full_unstemmed Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma
title_short Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma
title_sort application of a two-analyte integrated population pharmacokinetic model to evaluate the impact of intrinsic and extrinsic factors on the pharmacokinetics of polatuzumab vedotin in patients with non-hodgkin lymphoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708381/
https://www.ncbi.nlm.nih.gov/pubmed/33258982
http://dx.doi.org/10.1007/s11095-020-02933-6
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