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Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma
This population pharmacokinetics analysis evaluated the target-mediated drug disposition of inotuzumab ozogamicin (InO) through an empirical time-dependent clearance (CL(t)) term and identified potential covariates that may be important predictors of variability in InO distribution and elimination....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529376/ https://www.ncbi.nlm.nih.gov/pubmed/30859374 http://dx.doi.org/10.1007/s10928-018-9614-9 |
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author | Garrett, May Ruiz-Garcia, Ana Parivar, Kourosh Hee, Brian Boni, Joseph |
author_facet | Garrett, May Ruiz-Garcia, Ana Parivar, Kourosh Hee, Brian Boni, Joseph |
author_sort | Garrett, May |
collection | PubMed |
description | This population pharmacokinetics analysis evaluated the target-mediated drug disposition of inotuzumab ozogamicin (InO) through an empirical time-dependent clearance (CL(t)) term and identified potential covariates that may be important predictors of variability in InO distribution and elimination. This analysis was conducted by pooling data from 2 studies of single-agent InO in patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (ALL), 3 studies of single-agent InO, 5 studies of InO plus rituximab (R-InO), and 1 study of R-InO plus chemotherapy in patients with R/R B-cell non-Hodgkin lymphoma (NHL). Pharmacokinetic data included 8361 InO concentration–time observations that were modeled using nonlinear mixed-effects analysis. Covariate relations were identified using generalized additive modeling on base model parameters and then tested in a stepwise manner via covariate modeling. InO concentration was described with a 2-compartment model with linear and time-dependent clearance components. Based on the final model, baseline body surface area was a covariate of the linear and time-dependent clearance components and volume of distribution in the central compartment; baseline percentage of blasts in the peripheral blood was a covariate of the decay coefficient of the time-dependent clearance term (CL(t)); and concomitant rituximab treatment was a covariate of the linear clearance component (CL(1)). The magnitude of change of each pharmacokinetic parameter due to these covariates was not considered clinically relevant. Therefore, no dose adjustment of InO for the treatment of patients with R/R B-cell ALL or NHL is needed on the basis of selected covariates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10928-018-9614-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6529376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-65293762019-06-07 Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma Garrett, May Ruiz-Garcia, Ana Parivar, Kourosh Hee, Brian Boni, Joseph J Pharmacokinet Pharmacodyn Original Paper This population pharmacokinetics analysis evaluated the target-mediated drug disposition of inotuzumab ozogamicin (InO) through an empirical time-dependent clearance (CL(t)) term and identified potential covariates that may be important predictors of variability in InO distribution and elimination. This analysis was conducted by pooling data from 2 studies of single-agent InO in patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (ALL), 3 studies of single-agent InO, 5 studies of InO plus rituximab (R-InO), and 1 study of R-InO plus chemotherapy in patients with R/R B-cell non-Hodgkin lymphoma (NHL). Pharmacokinetic data included 8361 InO concentration–time observations that were modeled using nonlinear mixed-effects analysis. Covariate relations were identified using generalized additive modeling on base model parameters and then tested in a stepwise manner via covariate modeling. InO concentration was described with a 2-compartment model with linear and time-dependent clearance components. Based on the final model, baseline body surface area was a covariate of the linear and time-dependent clearance components and volume of distribution in the central compartment; baseline percentage of blasts in the peripheral blood was a covariate of the decay coefficient of the time-dependent clearance term (CL(t)); and concomitant rituximab treatment was a covariate of the linear clearance component (CL(1)). The magnitude of change of each pharmacokinetic parameter due to these covariates was not considered clinically relevant. Therefore, no dose adjustment of InO for the treatment of patients with R/R B-cell ALL or NHL is needed on the basis of selected covariates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10928-018-9614-9) contains supplementary material, which is available to authorized users. Springer US 2019-03-11 2019 /pmc/articles/PMC6529376/ /pubmed/30859374 http://dx.doi.org/10.1007/s10928-018-9614-9 Text en © Pfizer 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Paper Garrett, May Ruiz-Garcia, Ana Parivar, Kourosh Hee, Brian Boni, Joseph Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma |
title | Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma |
title_full | Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma |
title_fullStr | Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma |
title_full_unstemmed | Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma |
title_short | Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma |
title_sort | population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-hodgkin lymphoma |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529376/ https://www.ncbi.nlm.nih.gov/pubmed/30859374 http://dx.doi.org/10.1007/s10928-018-9614-9 |
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