Cargando…
Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC
Pazopanib is a potent multi-targeted kinase inhibitor approved for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib is characterized by a significant inter- and intra-patient variability and a target through plasma concentration of 20.5 mg·L(−...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469080/ https://www.ncbi.nlm.nih.gov/pubmed/34577627 http://dx.doi.org/10.3390/ph14090927 |
_version_ | 1784573838696120320 |
---|---|
author | Ozbey, Agustos Cetin Combarel, David Poinsignon, Vianney Lovera, Christine Saada, Esma Mir, Olivier Paci, Angelo |
author_facet | Ozbey, Agustos Cetin Combarel, David Poinsignon, Vianney Lovera, Christine Saada, Esma Mir, Olivier Paci, Angelo |
author_sort | Ozbey, Agustos Cetin |
collection | PubMed |
description | Pazopanib is a potent multi-targeted kinase inhibitor approved for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib is characterized by a significant inter- and intra-patient variability and a target through plasma concentration of 20.5 mg·L(−1). However, routine monitoring of trough plasma concentrations at fixed hours is difficult in daily practice. Herein, we aimed to characterize the pharmacokinetic (PK) profile of pazopanib and to identify a target area under the curve (AUC) more easily extrapolated from blood samples obtained at various timings after drug intake. A population pharmacokinetic (popPK) model was constructed to analyze pazopanib PK and to estimate the pazopanib clearance of a patient regardless of the time of sampling. Data from the therapeutic drug monitoring (TDM) of patients with cancer at Institute Gustave Roussy and a clinical study (phase I/II) that evaluates the tolerance to pazopanib were used. From the individual clearance, it is then possible to obtain the patient’s AUC. A target AUC for maximum efficacy and minimum side effects of 750 mg·h·L(−1) was determined. The comparison of the estimated AUC with the target AUC would enable us to determine whether plasma exposure is adequate or whether it would be necessary to propose therapeutic adjustments. |
format | Online Article Text |
id | pubmed-8469080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84690802021-09-27 Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC Ozbey, Agustos Cetin Combarel, David Poinsignon, Vianney Lovera, Christine Saada, Esma Mir, Olivier Paci, Angelo Pharmaceuticals (Basel) Article Pazopanib is a potent multi-targeted kinase inhibitor approved for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib is characterized by a significant inter- and intra-patient variability and a target through plasma concentration of 20.5 mg·L(−1). However, routine monitoring of trough plasma concentrations at fixed hours is difficult in daily practice. Herein, we aimed to characterize the pharmacokinetic (PK) profile of pazopanib and to identify a target area under the curve (AUC) more easily extrapolated from blood samples obtained at various timings after drug intake. A population pharmacokinetic (popPK) model was constructed to analyze pazopanib PK and to estimate the pazopanib clearance of a patient regardless of the time of sampling. Data from the therapeutic drug monitoring (TDM) of patients with cancer at Institute Gustave Roussy and a clinical study (phase I/II) that evaluates the tolerance to pazopanib were used. From the individual clearance, it is then possible to obtain the patient’s AUC. A target AUC for maximum efficacy and minimum side effects of 750 mg·h·L(−1) was determined. The comparison of the estimated AUC with the target AUC would enable us to determine whether plasma exposure is adequate or whether it would be necessary to propose therapeutic adjustments. MDPI 2021-09-15 /pmc/articles/PMC8469080/ /pubmed/34577627 http://dx.doi.org/10.3390/ph14090927 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ozbey, Agustos Cetin Combarel, David Poinsignon, Vianney Lovera, Christine Saada, Esma Mir, Olivier Paci, Angelo Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC |
title | Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC |
title_full | Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC |
title_fullStr | Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC |
title_full_unstemmed | Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC |
title_short | Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC |
title_sort | population pharmacokinetic analysis of pazopanib in patients and determination of target auc |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469080/ https://www.ncbi.nlm.nih.gov/pubmed/34577627 http://dx.doi.org/10.3390/ph14090927 |
work_keys_str_mv | AT ozbeyagustoscetin populationpharmacokineticanalysisofpazopanibinpatientsanddeterminationoftargetauc AT combareldavid populationpharmacokineticanalysisofpazopanibinpatientsanddeterminationoftargetauc AT poinsignonvianney populationpharmacokineticanalysisofpazopanibinpatientsanddeterminationoftargetauc AT loverachristine populationpharmacokineticanalysisofpazopanibinpatientsanddeterminationoftargetauc AT saadaesma populationpharmacokineticanalysisofpazopanibinpatientsanddeterminationoftargetauc AT mirolivier populationpharmacokineticanalysisofpazopanibinpatientsanddeterminationoftargetauc AT paciangelo populationpharmacokineticanalysisofpazopanibinpatientsanddeterminationoftargetauc |